Small nucleolar RNAs(snoRNAs)were previously regarded as a class of functionally conserved housekeeping genes,primarily involved in the regulation of ribosome biogenesis by ribosomal RNA(rRNA)modification.However,some...Small nucleolar RNAs(snoRNAs)were previously regarded as a class of functionally conserved housekeeping genes,primarily involved in the regulation of ribosome biogenesis by ribosomal RNA(rRNA)modification.However,some of them are involved in several biological processes via complex molecular mechanisms.DNA damage response(DDR)is a conserved mechanism for maintaining genomic stability to prevent the occurrence of various human diseases.It has recently been revealed that snoRNAs are involved in DDR at multiple levels,indicating their relevant theoretical and clinical significance in this field.The present review systematically addresses four main points,including the biosynthesis and classification of snoRNAs,the mechanisms through which snoRNAs regulate target molecules,snoRNAs in the process of DDR,and the significance of snoRNA in disease diagnosis and treatment.It focuses on the potential functions of snoRNAs in DDR to help in the discovery of the roles of snoRNAs in maintaining genome stability and pathological processes.展开更多
By using the DNA specific cytochemical staining method (NAMA_Ur) and conventional electron microscopic technique, the authors examined the configuration of intranucleolar DNA in Allium cepa L. cells and found that...By using the DNA specific cytochemical staining method (NAMA_Ur) and conventional electron microscopic technique, the authors examined the configuration of intranucleolar DNA in Allium cepa L. cells and found that nucleolar DNA within the fibrillar center (FC) underwent a structural transformation process from condensed to extended state. The authors' observations also displayed a continuous arrangement process of nucleolar DNA, i.e., the extranucleolar DNA entered FC through the nucleolar organizer region (NOR) channel, then extended to the periphery of FC or to the border between FC and dense fibrillar component (DFC), and distributed along the periphery of FC. Thence, by passing through the NOR channel between FCs, the nucleolar DNA continued to transfer to other FCs and arranged in the same above_mentioned forms.展开更多
Human normal endometrium was examined in ultrathin sections. Nucleolar channel system (NCS) appeared in the endometrial epithelial cells during the early and mid secretory phase of menstrual cycle. The NCS was a hollo...Human normal endometrium was examined in ultrathin sections. Nucleolar channel system (NCS) appeared in the endometrial epithelial cells during the early and mid secretory phase of menstrual cycle. The NCS was a hollow ball like structure of different sizes and was composed of 2 to 5 rows of tubules embedded in an amorphous matrix. On its surface there were numerous electron dense particles resembling ribosonies. It was usually located within or associated with the nucleolus. Sometimes, it was close to the nuclear envelope or protruding out from the nucleus. On occasion, NCS with simplified structure was found in the perinuclear cytoplasm. Concepts concerning the genesis, involution and function(s) of the NCS were discussed.展开更多
Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular funct...Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular functions related to protein synthesis.SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression,holding immense potential in controlling human diseases.It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types,stages,metastasis,treatment response and/or prognosis in patients.On the other hand,colorectal cancer(CRC),a prevalent malignancy of the digestive system,is characterized by high incidence and mortality rates,ranking as the third most common cancer type.Recent research indicates that snoRNA dysregulation is associated with CRC,as snoRNA expression significantly differs between normal and cancerous conditions.Consequently,assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC.Nevertheless,current comprehension of the potential roles of snoRNAs in CRC remains limited.This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC,providing valuable insights into the discovery of novel biomarkers,therapeutic targets,and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.展开更多
Objective To determine whether formation of the nucleolar channel system (NCS) in human endometrium depends on the presence of progesteronal steroids. Materials & Methods Tissues of late proliferative endometrium ...Objective To determine whether formation of the nucleolar channel system (NCS) in human endometrium depends on the presence of progesteronal steroids. Materials & Methods Tissues of late proliferative endometrium were obtained from 5 normally cycling women of reproductive age. Half of each tissue was cultured in the DMEM medium containing diethylstilbesterol (25 μg/mL) plus medroxyprogesterone acetate (25 μg/mL) (E + P culture). As a control, the other half was cultured in the medium alone. After 100 h incubation, the tissues were assessed for the formation of NCS with transmission electron microscope.Results NCS was observed in the endometrial epithelium treated with E + P or the medium alone. Moreover, giant mitochondria and glycogen accumulation were both seen in epithelia derived from both types of cultures.Conclusion Progesterone would be not indispensable for the formation of NCS in human endometrium. Transition of proliferative endometrium to the secretory stage in vitro could occur even in the absence of both estrogen and progesterone.展开更多
Cancer has become the most life-threatening disease in the world.Mutations in and aberrant expression of genes encoding proteins and mutations in noncoding RNAs,especially long noncoding RNAs(lncRNAs),have significant...Cancer has become the most life-threatening disease in the world.Mutations in and aberrant expression of genes encoding proteins and mutations in noncoding RNAs,especially long noncoding RNAs(lncRNAs),have significant effects in human cancers.LncRNAs have no protein-coding ability but function extensively in numerous physiological and pathological processes.Small nucleolar RNA host gene 3(SNHG3)is a novel lncRNA and has been reported to be differentially expressed in various tumors,such as liver cancer,gastric cancer,and glioma.However,the interaction mechanisms for the regulation between SNHG3 and tumor progression are poorly understood.In this review,we summarize the results of SNHG3 studies in humans,animal models,and cells to underline the expression and role of SNHG3 in cancer.SNHG3 expression is upregulated in most tumors and is detrimental to patient prognosis.SNHG3 expression in lung adenocarcinoma remains controversial.Concurrently,SNHG3 affects oncogenes and tumor suppressor genes through various mechanisms,including competing endogenous RNA effects.A deeper understanding of the contribution of SNHG3 in clinical applications and tumor development may provide a new target for cancer diagnosis and treatment.展开更多
By using silver colloid staining technique,nucleolar organizer region-associated proteins(AgNORs)were studied quantatively in paraffin sections of 12 casesof polypoid adenomas,10 cases of villous adenomas,22 cases of ...By using silver colloid staining technique,nucleolar organizer region-associated proteins(AgNORs)were studied quantatively in paraffin sections of 12 casesof polypoid adenomas,10 cases of villous adenomas,22 cases of colonadenocarcinomas,and 10 cases of normal colonic mucosa as control.The resultsshowed that the mean number of AgNORs per nucleus in the villous adcnoma was similarto that of adenocaranoma,which significantly exceeded those of the normal mucosa andthe polypoid adenoma.The granules of AgNORs in adcnocarcinoma were much largerand more irregular in sizc and shape.It is suggested that benign villous adenoma is akind of lesion between polypoid adenoma and adenocarcinoma,and AgNOR techniquemay be very helpful in differential diagnosis of colon tumors.展开更多
The present work studied the application of AgNOR count to differential diagnosis between cutaneous T cell lymphoma (CTCL) and cutaneous pseudolymphoma (CPL). Paraffin sections from 50 mycosis fungoides (22 MFI-Premyc...The present work studied the application of AgNOR count to differential diagnosis between cutaneous T cell lymphoma (CTCL) and cutaneous pseudolymphoma (CPL). Paraffin sections from 50 mycosis fungoides (22 MFI-Premycotic stage, 24 MF Ⅰ infiltrative stage and 4 MF Ⅲ - tumor stage), 2 nonepidermotropic cutaneous T cell lymphoma (NECTCL) and 9 CPL were investigated. In each case, 200 cells randomly selected were examined using a × 100 oil immersion lens. The mean number, standard deviation and standard error of the mean of AgNOR counts were as follows: MFⅠ 1.17±0.09, SEM = 0.01; MⅡ 1.17±0.01, SEM = 0.01; MF Ⅲ. 3.55±0.87, SEM = 0.43; NECTCL 4.5±0.28, SEM -0.199; CPL 1.17±0.1, SEM ± 0.03. The results revealed a highly significant difference between CTCL (MFⅢ+NECTCL) and CPL (t = 4.75, P<0.001), tumor stage (MF Ⅲ) and pretumor stage (MFI, MF Ⅱ) of mycosis fungoides (t = 4.75, P<0.001). Thus. AgNOR count is valuable in differential diagnosis.展开更多
Objective： To evaluate the relation between argyrophilic nucleolar organizer region （AgNOR）-associated proteins and clinicopathological parameters and survival in non-small-cell lung cancer （NSCLC）. Methods： A t...Objective： To evaluate the relation between argyrophilic nucleolar organizer region （AgNOR）-associated proteins and clinicopathological parameters and survival in non-small-cell lung cancer （NSCLC）. Methods： A total of 207 surgical specimens diagnosed as NSCLC were included in this study. Double-staining procedures were performed using antigen Ki-67 （clone MIB-1） and silver nitrate by immunohistochemical and AgNOR-staining methods. Results： The AgNOR area in MIB-l-positive cells of NSCLC is related to clinicopathological parameters under the TNM （tumor, node, and metastasis） system. The survival of patients with small AgNOR area in MIB-1-positive cells is better than that of patients with large AgNOR area. Molecular, biological （AgNOR area in MIB-l-positive cells）, and clinicopathological （greatest tumor dimension, metastases to regional lymph nodes, histology, and differentiation） parameters are independent prognostic factors of NSCLC.Conclusion： The AgNOR area in MIB- 1-positive cells is related to clinicopathological parameters and survival in NSCLC.展开更多
The argyrophil method for nucleolar organizer regions (AgNOR) known as the AgNor technique and mucin histochemical stain were applied to Investigate the dysplasia and cancaration in ulcerative colitis Including 58 cas...The argyrophil method for nucleolar organizer regions (AgNOR) known as the AgNor technique and mucin histochemical stain were applied to Investigate the dysplasia and cancaration in ulcerative colitis Including 58 cases of biopsy specimens and three cases operative specimens. The numbers of AgNOR have been gradully increased with the grades of dasplasls. Similarly the percentage of sialomucin having vicinal diols on side chain of sialic acid also gradully Increased with the grades of dysplasia. The AgNOR reflects rDNA transcriptional activity responsible for degrees of differentiation of cell. Epithelial cells secreting a heterogeneous mucin, could be taken as a signal of abnormal cellular differentiation. AgNOR and mucln chages might be assumed as a criteria In representing malignant transformation.展开更多
This editorial reviews the molecular mechanisms underlying the roles of the long non-coding RNA(lncRNA)small nucleolar RNA host gene 16(SNHG16)in digestive system cancers based on two recent studies on lncRNAs in dige...This editorial reviews the molecular mechanisms underlying the roles of the long non-coding RNA(lncRNA)small nucleolar RNA host gene 16(SNHG16)in digestive system cancers based on two recent studies on lncRNAs in digestive system tumors.The first study,by Zhao et al,explored how hBD-1 affects colon cancer,via the lncRNA TCONS_00014506,by inhibiting mTOR and promoting autophagy.The second one,by Li et al,identified the lncRNA prion protein testis specific(PRNT)as a factor in oxaliplatin resistance by sponging ZNF184 to regulate HIPK2 and influence colorectal cancer progression and chemoresistance,suggesting PRNT as a potential therapeutic target for colorectal cancer.Both of these two articles discuss the mechanisms by which lncRNAs contribute to the development and progression of digestive system cancers.As a recent research hotspot,SNHG16 is a typical lncRNA that has been extensively studied for its association with digestive system cancers.The prevailing hypothesis is that SNHG16 participates in the development and progression of digestive system tumors by acting as a competing endogenous RNA,interacting with other proteins,regulating various genes,and affecting downstream target molecules.This review systematically examines the recently reported biological functions,related molecular mechanisms,and potential clinical significance of SNHG16 in various digestive system cancers,and explores the relationship between SNHG16 and digestive system cancers.The findings suggest that SNHG16 may serve as a potential biomarker and therapeutic target for human digestive system cancers.展开更多
AIM: To investigate the subcellular localization and the function of mouse transducin β-like 3(Tbl3).METHODS: The coding sequence of mouse Tbl3 was cloned from the c DNAs of a promyelocyte cell line by reverse transc...AIM: To investigate the subcellular localization and the function of mouse transducin β-like 3(Tbl3).METHODS: The coding sequence of mouse Tbl3 was cloned from the c DNAs of a promyelocyte cell line by reverse transcription-polymerase chain reaction. Fusion constructs of Tbl3 and enhanced green fluorescent protein(EGFP) were transfected into fibroblasts and examined by fluorescence microscopy to reveal the subcellular localization of tbl3. To search for nucleolar targeting sequences, scanning deletions of Tbl3-EGFP were constructed and transfected into fibroblasts. To explore the possible function of Tbl3, small hairpin RNAs(sh RNAs) were used to knock down endogenous Tbl3 in mouse promyelocytes and fibroblasts. The effects of Tbl3 knockdown on ribosomal RNA(r RNAs) synthesis or processing were studied by labeling cells with 5,6-3H-uridine followed by a chase with fresh medium for various periods. Total RNAs were purified from treated cells and subjected to gel electrophoresis and Northern analysis. Ribosome profiling by sucrose gradient centrifugation was used to compare the amounts of 40 S and 60 S ribosome subunits as well as the 80 S monosome. The impact of Tbl3 knockdown on cell growth and proliferation was examined by growth curves and colony assays.RESULTS: The largest open reading frame of mouse Tbl3 encodes a protein of 801 amino acids(AA) with an apparent molecular weight of 89-90 kilodalton. It contains thirteen WD40 repeats(an ancient protein-protein interaction motif) and a carboxyl terminus that is highly homologous to the corresponding region of the yeast nucleolar protein, utp13. Virtually nothing is known about the biological function of Tbl3. All cell lines surveyed expressed Tbl3 and the level of expression correlated roughly with cell proliferation and/or biosynthetic activity. Using Tbl3-EGFP fusion constructs we obtained the first direct evidence that Tbl3 is targeted to the nucleoli in mammalian cells. However, no previously described nucleolar targeting sequences were found in Tbl3, suggesting that the WD40 motif and/or other topological features are responsible for nucleolar targeting. Partial knockdown(by 50%-70%) of mouse Tbl3 by shR NA had no discernable effects on the processing of the 47 S pre-ribosomal RNA(pre-r RNA) or the steady-state levels of the mature 28 S, 18 S and 5.8S r RNAs but consistently increased the expression level of the 47 S pre-rR NA by two to four folds. The results of the current study corroborated the previous finding that there was no detectable rR NA processing defects in zebra fish embryos with homozygous deletions of zebra fish Tbl3. As ribosome production consumes the bulk of cellular energy and biosynthetic precursors, dysregulation of pre-rR NA synthesis can have negative effects on cell growth, proliferation and differentiation. Indeed, partial knockdown of Tbl3 in promyelocytes severely impaired their proliferation. The inhibitory effect of Tbl3 knockdown was also observed in fibroblasts, resulting in an 80% reduction in colony formation. Taken together, these results indicate that Tbl3 is a newly recognized nucleolar protein with regulatory roles at very early stages of ribosome biogenesis, perhaps at the level of rR NA gene transcription. CONCLUSION: Tbl3 is a newly recognized nucleolar protein with important regulatory roles in ribosome biogenesis.展开更多
Small nucleolar RNAs (snoRNAs) are non-coding RNA (ncRNA) molecules,which are associated with specific proteins to form small nucleolar ribonucleoparticles.However,the function of snoRNAs in cancer still remains elusi...Small nucleolar RNAs (snoRNAs) are non-coding RNA (ncRNA) molecules,which are associated with specific proteins to form small nucleolar ribonucleoparticles.However,the function of snoRNAs in cancer still remains elusive.Recently,several independent lines of evidence have indicated that these ncRNAs might have crucial roles in controlling tumorigenesis,and snoRNAs could be potential biomarkers for cancer.展开更多
Dear Editor,Transfer RNA(tRNA)is an indispensable adaptor molecule in the messenger RNA(mRNA)translation machinery,facilitating the conversion of genetic information encoded in mRNA into functional proteins.Numerous p...Dear Editor,Transfer RNA(tRNA)is an indispensable adaptor molecule in the messenger RNA(mRNA)translation machinery,facilitating the conversion of genetic information encoded in mRNA into functional proteins.Numerous posttranscriptional modifications in tRNA have been identified,which play significantroles in modulating tRNA folding,biochemical stability,amino-acylation,and codon–anticodon interaction(Suzuki,2021).TRMT10A,the mammalian homolog of Trm10,incorporates N1-methylguanosine modification at position 9(m1G9)of various cytoplasmic tRNAs,including tRNAGln and tRNAIniMeth(Vilardo et al.,2020).Mutations in human TRMT10A,which is enriched in pancreatic islets and brain(Igoillo-Esteve et al.,2013),are often associated with microcephaly,intellectual disability,early-onset diabetes,and short stature(Igoillo-Esteve et al.,2013;Uçan Tokuçet al.,2024).展开更多
Purified nucleoli of HeLa cells were treated sequentially with nonionic detergent, nucleic acid enzyme, low salt and high salt. The residual nucleolar structure termed nucleolar skeleton (nucleolar matrix) was shown a...Purified nucleoli of HeLa cells were treated sequentially with nonionic detergent, nucleic acid enzyme, low salt and high salt. The residual nucleolar structure termed nucleolar skeleton (nucleolar matrix) was shown as a fine network under electron microscope with DGD embedding-unembedding technique. Such structures of BHK-21 cell and mouse liver cell are similar to that of HeLa cell. The protein composition of the nucleolar skeleton of HeLa cells was analyzed. The protein composition of such nucleolar residual shows obvious difference from the compositions of nuclear matrix and chromosome scaffold. The major protein composition of the nucleolar skeleton of HeLa cells contains 6-7 polypeptides. Their molecular weights are about 48, 43, 36 and 33 ku. Further studies show that actin and fib-rillarin are two major protein components of nucleolar skeleton of HeLa cells.展开更多
Accumulating evidence suggests that non-coding RNAs （ncRNAs） are both widespread and functionally important in many eukaryotic organisms. In this study, we employed a special size fractionation and cDNA library cons...Accumulating evidence suggests that non-coding RNAs （ncRNAs） are both widespread and functionally important in many eukaryotic organisms. In this study, we employed a special size fractionation and cDNA library construction method followed by 454 deep sequencing to systematically profile rice intermediate-size ncRNAs. Our analysis resulted in the identification of 1349 ncRNAs in total, including 754 novel ncRNAs of an unknown functional category. Chromosome distribution of all identified ncRNAs showed no strand bias, and displayed a pattern similar to that observed in protein-coding genes with few chromosome dependencies. More than half of the ncRNAs were centered around the plus-strand of the 5＇ and 3＇ termini of the coding regions. The majority of the novel ncRNAs were rice specific, while 78% of the small nucleolar RNAs （snoRNAs） were conserved. Tandem duplication drove the expansion of over half of the snoRNA gene families. Furthermore, 90% of the snoRNA candidates were shown to produce small RNAs between 20-30 nt, 80% of which were associated with ARGONAUT proteins generally, and AGOlb in particular. Overall, our findings provide a comprehensive view of an intermediate-size non-coding transcriptome in a monocot species, which will serve as a useful platform for an in-depth analysis of ncRNA functions.展开更多
LIN28 is an RNA binding protein with important roles in early embryo development,stem cell differentiation/re-programming,tumorigenesis and metabolism.Previous studies have focused mainly on its role in the cytosol wh...LIN28 is an RNA binding protein with important roles in early embryo development,stem cell differentiation/re-programming,tumorigenesis and metabolism.Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs,and few have addressed LIN28's role within the nucleus.Here,we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development.Maternal LIN28 expression drops upon exit from the 2-cell stage,and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blas-tocyst stage development,to become dominantly expressed in the cytosol after implantation.In cultured pluripotent stem cells(PSCs),loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes.Mechanistically,LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity,and its loss leads to nucleolar phase separation defects,ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux.LIN28 also resides in a complex containing the nucleolar factor Nucleolin(NCL)and the transcrip-tional repressor TRIM28,and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci,and thus de-repressed Dux and reduced rRNA expression.Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling,translationally inert and anabolically inactive state,which is a part of previously unappreciated 2C-like transcriptional program.These findings elucidate novel roles for nucleolar LIN28 in PSCs,and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.展开更多
Nucleolus, in which rRNA precursors are synthesized and subunits of ribosomesare assembled, is composed of many copies of rDNA, rRNA and many kinds ofproteins. The processing of rRNA precursors also occurs in nucleolu...Nucleolus, in which rRNA precursors are synthesized and subunits of ribosomesare assembled, is composed of many copies of rDNA, rRNA and many kinds ofproteins. The processing of rRNA precursors also occurs in nucleolus, which is associ-ated with some nonribosomal proteins. In the 1980s, scientists proposed thatnucleolar skeleton or nucleolar matrix which is mainly constructed with proteins展开更多
Background and Aims:Long non-coding RNA small nucleolar RNA host genes(SNHGs)play a critical role in the occurrence and development of tumors.In this study,we aimed to investigate the role of SNHG4 in hepatocellular c...Background and Aims:Long non-coding RNA small nucleolar RNA host genes(SNHGs)play a critical role in the occurrence and development of tumors.In this study,we aimed to investigate the role of SNHG4 in hepatocellular carcinoma(HCC)and its underlining mechanism.Methods:Datasets were acquired from The Cancer Genome Atlas(TCGA)database.lncLocator 2.0 was used to identify the distribution of SNHG4 in HCC cells.Gene expression,Kaplan-Meier survival,microRNA and transcription factor target analyses were performed with the University of Alabama Cancer(UALCAN)Database,Kaplan-Meier Plotter,LinkedOmics,WebGestalt and gene set enrichment analysis,respectively.Gene Ontology and pathway enrichment analyses and assessment of RNA binding proteins were performed by R software,circlncRNAnet and Encyclopedia of RNA Interactomes(EN-CORI).In addition,CirclncRNAnet and ENCORI were used to find the correlation between SNHG4 and important proteins,while the prognostic value was assessed with the Human Protein Atlas database and Kaplan-Meier Plotter.Results:Expression of SNHG4 in HCC is higher in HCC tissue than in normal healthy liver tissues and is mainly distributed in the nucleus.SNHG4 positively correlated with poor prognosis(p<0.01 for overall survival and recurrence-free survival).Functional enrichment analysis revealed SNHG4 involve-ment with regulation of ribosomal RNA synthesis and the RNA processing and surveillance pathway.SNHG4 is closely associated with miR-154 and miR-206,transcription factor target E2F family and the signaling pathway for MAPK/ERK and mTOR.U2 auxiliary factor 2(U2AF2)showed strong correlation with SNHG4,while low-expression of U2AF2 showed good prognosis.Conclusions:Based on our find-ings,we infer SNHG4 may play a role in the formation of HCC via regulation of tumor-related pathways.展开更多
Human NUDT16(hNUDT16)is a decapping enzyme initially identified as the human homolog to the Xenopus laevis X29.As a metalloenzyme,hNUDT16 relies on divalent cations for its cap-hydrolysis activity to remove m7 GDP and...Human NUDT16(hNUDT16)is a decapping enzyme initially identified as the human homolog to the Xenopus laevis X29.As a metalloenzyme,hNUDT16 relies on divalent cations for its cap-hydrolysis activity to remove m7 GDP and m227GDP from RNAs.Metal also determines substrate specificity of the enzyme.So far,only U8 small nucleolar RNA(snoRNA)has been identified as the substrate of hNUDT16 in the presence of Mg2+.Here we demonstrate that besides U8,hNUDT16 can also actively cleave the m7 GDP cap from mRNAs in the presence of Mg2+or Mn2+.We further show that hNUDT16 does not preferentially recognize U8 or mRNA substrates by our cross-inhibition and quantitative decapping assays.In addition,our mutagenesis analysis identifies several key residues involved in hydrolysis and confirms the key role of the REXXEE motif in catalysis.Finally an investigation into the subcellular localization of hNUDT16 revealed its abundance in both cytoplasm and nucleus.These findings extend the substrate spectrum of hNUDT16 beyond snoRNAs to also include mRNA,demonstrating the pleiotropic decapping activity of hNUDT16.展开更多
基金supported by the National Natural Science Foundation of China(32071240,82373526).
文摘Small nucleolar RNAs(snoRNAs)were previously regarded as a class of functionally conserved housekeeping genes,primarily involved in the regulation of ribosome biogenesis by ribosomal RNA(rRNA)modification.However,some of them are involved in several biological processes via complex molecular mechanisms.DNA damage response(DDR)is a conserved mechanism for maintaining genomic stability to prevent the occurrence of various human diseases.It has recently been revealed that snoRNAs are involved in DDR at multiple levels,indicating their relevant theoretical and clinical significance in this field.The present review systematically addresses four main points,including the biosynthesis and classification of snoRNAs,the mechanisms through which snoRNAs regulate target molecules,snoRNAs in the process of DDR,and the significance of snoRNA in disease diagnosis and treatment.It focuses on the potential functions of snoRNAs in DDR to help in the discovery of the roles of snoRNAs in maintaining genome stability and pathological processes.
文摘By using the DNA specific cytochemical staining method (NAMA_Ur) and conventional electron microscopic technique, the authors examined the configuration of intranucleolar DNA in Allium cepa L. cells and found that nucleolar DNA within the fibrillar center (FC) underwent a structural transformation process from condensed to extended state. The authors' observations also displayed a continuous arrangement process of nucleolar DNA, i.e., the extranucleolar DNA entered FC through the nucleolar organizer region (NOR) channel, then extended to the periphery of FC or to the border between FC and dense fibrillar component (DFC), and distributed along the periphery of FC. Thence, by passing through the NOR channel between FCs, the nucleolar DNA continued to transfer to other FCs and arranged in the same above_mentioned forms.
文摘Human normal endometrium was examined in ultrathin sections. Nucleolar channel system (NCS) appeared in the endometrial epithelial cells during the early and mid secretory phase of menstrual cycle. The NCS was a hollow ball like structure of different sizes and was composed of 2 to 5 rows of tubules embedded in an amorphous matrix. On its surface there were numerous electron dense particles resembling ribosonies. It was usually located within or associated with the nucleolus. Sometimes, it was close to the nuclear envelope or protruding out from the nucleus. On occasion, NCS with simplified structure was found in the perinuclear cytoplasm. Concepts concerning the genesis, involution and function(s) of the NCS were discussed.
基金the National Natural Science Foundation of China,No.82273457Guangdong Basic and Applied Basic Research Foundation,No.2021A1515012180 and No.2023A1515012762+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040and Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular functions related to protein synthesis.SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression,holding immense potential in controlling human diseases.It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types,stages,metastasis,treatment response and/or prognosis in patients.On the other hand,colorectal cancer(CRC),a prevalent malignancy of the digestive system,is characterized by high incidence and mortality rates,ranking as the third most common cancer type.Recent research indicates that snoRNA dysregulation is associated with CRC,as snoRNA expression significantly differs between normal and cancerous conditions.Consequently,assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC.Nevertheless,current comprehension of the potential roles of snoRNAs in CRC remains limited.This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC,providing valuable insights into the discovery of novel biomarkers,therapeutic targets,and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.
基金This study was supported by the National Science Fund of P.R.China (No.39970765)
文摘Objective To determine whether formation of the nucleolar channel system (NCS) in human endometrium depends on the presence of progesteronal steroids. Materials & Methods Tissues of late proliferative endometrium were obtained from 5 normally cycling women of reproductive age. Half of each tissue was cultured in the DMEM medium containing diethylstilbesterol (25 μg/mL) plus medroxyprogesterone acetate (25 μg/mL) (E + P culture). As a control, the other half was cultured in the medium alone. After 100 h incubation, the tissues were assessed for the formation of NCS with transmission electron microscope.Results NCS was observed in the endometrial epithelium treated with E + P or the medium alone. Moreover, giant mitochondria and glycogen accumulation were both seen in epithelia derived from both types of cultures.Conclusion Progesterone would be not indispensable for the formation of NCS in human endometrium. Transition of proliferative endometrium to the secretory stage in vitro could occur even in the absence of both estrogen and progesterone.
基金Supported by the National Science and Technology Major Project of China,No. 2018ZX10302206 and 2017ZX10202203
文摘Cancer has become the most life-threatening disease in the world.Mutations in and aberrant expression of genes encoding proteins and mutations in noncoding RNAs,especially long noncoding RNAs(lncRNAs),have significant effects in human cancers.LncRNAs have no protein-coding ability but function extensively in numerous physiological and pathological processes.Small nucleolar RNA host gene 3(SNHG3)is a novel lncRNA and has been reported to be differentially expressed in various tumors,such as liver cancer,gastric cancer,and glioma.However,the interaction mechanisms for the regulation between SNHG3 and tumor progression are poorly understood.In this review,we summarize the results of SNHG3 studies in humans,animal models,and cells to underline the expression and role of SNHG3 in cancer.SNHG3 expression is upregulated in most tumors and is detrimental to patient prognosis.SNHG3 expression in lung adenocarcinoma remains controversial.Concurrently,SNHG3 affects oncogenes and tumor suppressor genes through various mechanisms,including competing endogenous RNA effects.A deeper understanding of the contribution of SNHG3 in clinical applications and tumor development may provide a new target for cancer diagnosis and treatment.
文摘By using silver colloid staining technique,nucleolar organizer region-associated proteins(AgNORs)were studied quantatively in paraffin sections of 12 casesof polypoid adenomas,10 cases of villous adenomas,22 cases of colonadenocarcinomas,and 10 cases of normal colonic mucosa as control.The resultsshowed that the mean number of AgNORs per nucleus in the villous adcnoma was similarto that of adenocaranoma,which significantly exceeded those of the normal mucosa andthe polypoid adenoma.The granules of AgNORs in adcnocarcinoma were much largerand more irregular in sizc and shape.It is suggested that benign villous adenoma is akind of lesion between polypoid adenoma and adenocarcinoma,and AgNOR techniquemay be very helpful in differential diagnosis of colon tumors.
文摘The present work studied the application of AgNOR count to differential diagnosis between cutaneous T cell lymphoma (CTCL) and cutaneous pseudolymphoma (CPL). Paraffin sections from 50 mycosis fungoides (22 MFI-Premycotic stage, 24 MF Ⅰ infiltrative stage and 4 MF Ⅲ - tumor stage), 2 nonepidermotropic cutaneous T cell lymphoma (NECTCL) and 9 CPL were investigated. In each case, 200 cells randomly selected were examined using a × 100 oil immersion lens. The mean number, standard deviation and standard error of the mean of AgNOR counts were as follows: MFⅠ 1.17±0.09, SEM = 0.01; MⅡ 1.17±0.01, SEM = 0.01; MF Ⅲ. 3.55±0.87, SEM = 0.43; NECTCL 4.5±0.28, SEM -0.199; CPL 1.17±0.1, SEM ± 0.03. The results revealed a highly significant difference between CTCL (MFⅢ+NECTCL) and CPL (t = 4.75, P<0.001), tumor stage (MF Ⅲ) and pretumor stage (MFI, MF Ⅱ) of mycosis fungoides (t = 4.75, P<0.001). Thus. AgNOR count is valuable in differential diagnosis.
文摘Objective： To evaluate the relation between argyrophilic nucleolar organizer region （AgNOR）-associated proteins and clinicopathological parameters and survival in non-small-cell lung cancer （NSCLC）. Methods： A total of 207 surgical specimens diagnosed as NSCLC were included in this study. Double-staining procedures were performed using antigen Ki-67 （clone MIB-1） and silver nitrate by immunohistochemical and AgNOR-staining methods. Results： The AgNOR area in MIB-l-positive cells of NSCLC is related to clinicopathological parameters under the TNM （tumor, node, and metastasis） system. The survival of patients with small AgNOR area in MIB-1-positive cells is better than that of patients with large AgNOR area. Molecular, biological （AgNOR area in MIB-l-positive cells）, and clinicopathological （greatest tumor dimension, metastases to regional lymph nodes, histology, and differentiation） parameters are independent prognostic factors of NSCLC.Conclusion： The AgNOR area in MIB- 1-positive cells is related to clinicopathological parameters and survival in NSCLC.
文摘The argyrophil method for nucleolar organizer regions (AgNOR) known as the AgNor technique and mucin histochemical stain were applied to Investigate the dysplasia and cancaration in ulcerative colitis Including 58 cases of biopsy specimens and three cases operative specimens. The numbers of AgNOR have been gradully increased with the grades of dasplasls. Similarly the percentage of sialomucin having vicinal diols on side chain of sialic acid also gradully Increased with the grades of dysplasia. The AgNOR reflects rDNA transcriptional activity responsible for degrees of differentiation of cell. Epithelial cells secreting a heterogeneous mucin, could be taken as a signal of abnormal cellular differentiation. AgNOR and mucln chages might be assumed as a criteria In representing malignant transformation.
文摘This editorial reviews the molecular mechanisms underlying the roles of the long non-coding RNA(lncRNA)small nucleolar RNA host gene 16(SNHG16)in digestive system cancers based on two recent studies on lncRNAs in digestive system tumors.The first study,by Zhao et al,explored how hBD-1 affects colon cancer,via the lncRNA TCONS_00014506,by inhibiting mTOR and promoting autophagy.The second one,by Li et al,identified the lncRNA prion protein testis specific(PRNT)as a factor in oxaliplatin resistance by sponging ZNF184 to regulate HIPK2 and influence colorectal cancer progression and chemoresistance,suggesting PRNT as a potential therapeutic target for colorectal cancer.Both of these two articles discuss the mechanisms by which lncRNAs contribute to the development and progression of digestive system cancers.As a recent research hotspot,SNHG16 is a typical lncRNA that has been extensively studied for its association with digestive system cancers.The prevailing hypothesis is that SNHG16 participates in the development and progression of digestive system tumors by acting as a competing endogenous RNA,interacting with other proteins,regulating various genes,and affecting downstream target molecules.This review systematically examines the recently reported biological functions,related molecular mechanisms,and potential clinical significance of SNHG16 in various digestive system cancers,and explores the relationship between SNHG16 and digestive system cancers.The findings suggest that SNHG16 may serve as a potential biomarker and therapeutic target for human digestive system cancers.
基金Supported by In part by a grant from the St.Perres Fund,No.11-02011
文摘AIM: To investigate the subcellular localization and the function of mouse transducin β-like 3(Tbl3).METHODS: The coding sequence of mouse Tbl3 was cloned from the c DNAs of a promyelocyte cell line by reverse transcription-polymerase chain reaction. Fusion constructs of Tbl3 and enhanced green fluorescent protein(EGFP) were transfected into fibroblasts and examined by fluorescence microscopy to reveal the subcellular localization of tbl3. To search for nucleolar targeting sequences, scanning deletions of Tbl3-EGFP were constructed and transfected into fibroblasts. To explore the possible function of Tbl3, small hairpin RNAs(sh RNAs) were used to knock down endogenous Tbl3 in mouse promyelocytes and fibroblasts. The effects of Tbl3 knockdown on ribosomal RNA(r RNAs) synthesis or processing were studied by labeling cells with 5,6-3H-uridine followed by a chase with fresh medium for various periods. Total RNAs were purified from treated cells and subjected to gel electrophoresis and Northern analysis. Ribosome profiling by sucrose gradient centrifugation was used to compare the amounts of 40 S and 60 S ribosome subunits as well as the 80 S monosome. The impact of Tbl3 knockdown on cell growth and proliferation was examined by growth curves and colony assays.RESULTS: The largest open reading frame of mouse Tbl3 encodes a protein of 801 amino acids(AA) with an apparent molecular weight of 89-90 kilodalton. It contains thirteen WD40 repeats(an ancient protein-protein interaction motif) and a carboxyl terminus that is highly homologous to the corresponding region of the yeast nucleolar protein, utp13. Virtually nothing is known about the biological function of Tbl3. All cell lines surveyed expressed Tbl3 and the level of expression correlated roughly with cell proliferation and/or biosynthetic activity. Using Tbl3-EGFP fusion constructs we obtained the first direct evidence that Tbl3 is targeted to the nucleoli in mammalian cells. However, no previously described nucleolar targeting sequences were found in Tbl3, suggesting that the WD40 motif and/or other topological features are responsible for nucleolar targeting. Partial knockdown(by 50%-70%) of mouse Tbl3 by shR NA had no discernable effects on the processing of the 47 S pre-ribosomal RNA(pre-r RNA) or the steady-state levels of the mature 28 S, 18 S and 5.8S r RNAs but consistently increased the expression level of the 47 S pre-rR NA by two to four folds. The results of the current study corroborated the previous finding that there was no detectable rR NA processing defects in zebra fish embryos with homozygous deletions of zebra fish Tbl3. As ribosome production consumes the bulk of cellular energy and biosynthetic precursors, dysregulation of pre-rR NA synthesis can have negative effects on cell growth, proliferation and differentiation. Indeed, partial knockdown of Tbl3 in promyelocytes severely impaired their proliferation. The inhibitory effect of Tbl3 knockdown was also observed in fibroblasts, resulting in an 80% reduction in colony formation. Taken together, these results indicate that Tbl3 is a newly recognized nucleolar protein with regulatory roles at very early stages of ribosome biogenesis, perhaps at the level of rR NA gene transcription. CONCLUSION: Tbl3 is a newly recognized nucleolar protein with important regulatory roles in ribosome biogenesis.
文摘Small nucleolar RNAs (snoRNAs) are non-coding RNA (ncRNA) molecules,which are associated with specific proteins to form small nucleolar ribonucleoparticles.However,the function of snoRNAs in cancer still remains elusive.Recently,several independent lines of evidence have indicated that these ncRNAs might have crucial roles in controlling tumorigenesis,and snoRNAs could be potential biomarkers for cancer.
基金Supplementary material is available at Journal of Molecular Cell Biology online.This study was supported by grants from the National Natural Science Foundation of China(82230075 to D.G.32270159 to J.W.)+2 种基金Guangdong Basic and Applied Basic Research Foundation(2023A1515012613 to J.W.)Shenzhen Science and Technology Program(JCYJ20200109142201695 and KQTD20180411143323605 to D.G.,JCYJ20220530145608018 to J.W.)Shenzhen Key Laboratory of Systems Medicine for Inflammatory Diseases(ZDSYS20220606100803007 to J.W.).
文摘Dear Editor,Transfer RNA(tRNA)is an indispensable adaptor molecule in the messenger RNA(mRNA)translation machinery,facilitating the conversion of genetic information encoded in mRNA into functional proteins.Numerous posttranscriptional modifications in tRNA have been identified,which play significantroles in modulating tRNA folding,biochemical stability,amino-acylation,and codon–anticodon interaction(Suzuki,2021).TRMT10A,the mammalian homolog of Trm10,incorporates N1-methylguanosine modification at position 9(m1G9)of various cytoplasmic tRNAs,including tRNAGln and tRNAIniMeth(Vilardo et al.,2020).Mutations in human TRMT10A,which is enriched in pancreatic islets and brain(Igoillo-Esteve et al.,2013),are often associated with microcephaly,intellectual disability,early-onset diabetes,and short stature(Igoillo-Esteve et al.,2013;Uçan Tokuçet al.,2024).
文摘Purified nucleoli of HeLa cells were treated sequentially with nonionic detergent, nucleic acid enzyme, low salt and high salt. The residual nucleolar structure termed nucleolar skeleton (nucleolar matrix) was shown as a fine network under electron microscope with DGD embedding-unembedding technique. Such structures of BHK-21 cell and mouse liver cell are similar to that of HeLa cell. The protein composition of the nucleolar skeleton of HeLa cells was analyzed. The protein composition of such nucleolar residual shows obvious difference from the compositions of nuclear matrix and chromosome scaffold. The major protein composition of the nucleolar skeleton of HeLa cells contains 6-7 polypeptides. Their molecular weights are about 48, 43, 36 and 33 ku. Further studies show that actin and fib-rillarin are two major protein components of nucleolar skeleton of HeLa cells.
基金This work was supported by grants from National Basic Research Program of China （973 Program） （2012CB910900） National Natural Science Foundation of China （31171156, U1031001）+1 种基金the Ministry of Science and Technology of China （2011CB100101, 2009DFB30030, 2008AA022301） and the Ministry of Agriculture of China （2008ZX08012-005, 2009ZX08012-021 B）.We thank Dr. Ning Wei and Abigail Coplin for reading and commenting this manuscript. No conflict of interest declared.
文摘Accumulating evidence suggests that non-coding RNAs （ncRNAs） are both widespread and functionally important in many eukaryotic organisms. In this study, we employed a special size fractionation and cDNA library construction method followed by 454 deep sequencing to systematically profile rice intermediate-size ncRNAs. Our analysis resulted in the identification of 1349 ncRNAs in total, including 754 novel ncRNAs of an unknown functional category. Chromosome distribution of all identified ncRNAs showed no strand bias, and displayed a pattern similar to that observed in protein-coding genes with few chromosome dependencies. More than half of the ncRNAs were centered around the plus-strand of the 5＇ and 3＇ termini of the coding regions. The majority of the novel ncRNAs were rice specific, while 78% of the small nucleolar RNAs （snoRNAs） were conserved. Tandem duplication drove the expansion of over half of the snoRNA gene families. Furthermore, 90% of the snoRNA candidates were shown to produce small RNAs between 20-30 nt, 80% of which were associated with ARGONAUT proteins generally, and AGOlb in particular. Overall, our findings provide a comprehensive view of an intermediate-size non-coding transcriptome in a monocot species, which will serve as a useful platform for an in-depth analysis of ncRNA functions.
基金We thank Hengyu Fan,Dan Zhang,Jianzhong Sheng,Pengfei Xu and Hua Lu for discussing and sharing facilities.J.Z.is supported by the National Key Research and Development Program of China(2018YFA0107100,2018YFA0107103,2018YFC1005002)the National Natural Science Foundation projects of China(31871453,91857116)+3 种基金the Zhejiang Natural Science Foundation projects of China(LR19C120001)High-Performance Computing Platform in Center of Cryo-Electron Microscopy of Zhejiang University and core facilities,Zhejiang University School of Medicine.H.Y.is supported by the Zhejiang Natural Science Foundation Projects of China(Grant No.LQ21C120002)J.W.is supported by National Institutes of Health(HD097268)New York State Stem Cell Science(C32569GG).
文摘LIN28 is an RNA binding protein with important roles in early embryo development,stem cell differentiation/re-programming,tumorigenesis and metabolism.Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs,and few have addressed LIN28's role within the nucleus.Here,we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development.Maternal LIN28 expression drops upon exit from the 2-cell stage,and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blas-tocyst stage development,to become dominantly expressed in the cytosol after implantation.In cultured pluripotent stem cells(PSCs),loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes.Mechanistically,LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity,and its loss leads to nucleolar phase separation defects,ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux.LIN28 also resides in a complex containing the nucleolar factor Nucleolin(NCL)and the transcrip-tional repressor TRIM28,and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci,and thus de-repressed Dux and reduced rRNA expression.Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling,translationally inert and anabolically inactive state,which is a part of previously unappreciated 2C-like transcriptional program.These findings elucidate novel roles for nucleolar LIN28 in PSCs,and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
文摘Nucleolus, in which rRNA precursors are synthesized and subunits of ribosomesare assembled, is composed of many copies of rDNA, rRNA and many kinds ofproteins. The processing of rRNA precursors also occurs in nucleolus, which is associ-ated with some nonribosomal proteins. In the 1980s, scientists proposed thatnucleolar skeleton or nucleolar matrix which is mainly constructed with proteins
基金supported by grants from the National key research and development program(2018YFC1315400)the National Natural Science Foundation of China(Nos.81773176,81870449).
文摘Background and Aims:Long non-coding RNA small nucleolar RNA host genes(SNHGs)play a critical role in the occurrence and development of tumors.In this study,we aimed to investigate the role of SNHG4 in hepatocellular carcinoma(HCC)and its underlining mechanism.Methods:Datasets were acquired from The Cancer Genome Atlas(TCGA)database.lncLocator 2.0 was used to identify the distribution of SNHG4 in HCC cells.Gene expression,Kaplan-Meier survival,microRNA and transcription factor target analyses were performed with the University of Alabama Cancer(UALCAN)Database,Kaplan-Meier Plotter,LinkedOmics,WebGestalt and gene set enrichment analysis,respectively.Gene Ontology and pathway enrichment analyses and assessment of RNA binding proteins were performed by R software,circlncRNAnet and Encyclopedia of RNA Interactomes(EN-CORI).In addition,CirclncRNAnet and ENCORI were used to find the correlation between SNHG4 and important proteins,while the prognostic value was assessed with the Human Protein Atlas database and Kaplan-Meier Plotter.Results:Expression of SNHG4 in HCC is higher in HCC tissue than in normal healthy liver tissues and is mainly distributed in the nucleus.SNHG4 positively correlated with poor prognosis(p<0.01 for overall survival and recurrence-free survival).Functional enrichment analysis revealed SNHG4 involve-ment with regulation of ribosomal RNA synthesis and the RNA processing and surveillance pathway.SNHG4 is closely associated with miR-154 and miR-206,transcription factor target E2F family and the signaling pathway for MAPK/ERK and mTOR.U2 auxiliary factor 2(U2AF2)showed strong correlation with SNHG4,while low-expression of U2AF2 showed good prognosis.Conclusions:Based on our find-ings,we infer SNHG4 may play a role in the formation of HCC via regulation of tumor-related pathways.
基金the Natural Science Foundation of China(No.30870118)。
文摘Human NUDT16(hNUDT16)is a decapping enzyme initially identified as the human homolog to the Xenopus laevis X29.As a metalloenzyme,hNUDT16 relies on divalent cations for its cap-hydrolysis activity to remove m7 GDP and m227GDP from RNAs.Metal also determines substrate specificity of the enzyme.So far,only U8 small nucleolar RNA(snoRNA)has been identified as the substrate of hNUDT16 in the presence of Mg2+.Here we demonstrate that besides U8,hNUDT16 can also actively cleave the m7 GDP cap from mRNAs in the presence of Mg2+or Mn2+.We further show that hNUDT16 does not preferentially recognize U8 or mRNA substrates by our cross-inhibition and quantitative decapping assays.In addition,our mutagenesis analysis identifies several key residues involved in hydrolysis and confirms the key role of the REXXEE motif in catalysis.Finally an investigation into the subcellular localization of hNUDT16 revealed its abundance in both cytoplasm and nucleus.These findings extend the substrate spectrum of hNUDT16 beyond snoRNAs to also include mRNA,demonstrating the pleiotropic decapping activity of hNUDT16.
