Selenocysteine (Sec) tRNAs serve as carrier molecules for the biosynthesis of Sec from serine and to donate Sec to protein in response to specific UGA codons. In this study, we describe the current status of Sec tRNAs...Selenocysteine (Sec) tRNAs serve as carrier molecules for the biosynthesis of Sec from serine and to donate Sec to protein in response to specific UGA codons. In this study, we describe the current status of Sec tRNAs in higher animals and further we exarnine: (i) the Sec tRNA population in Drosophila; (ii) transcription of the Sec tRNA in vivo (in Xenopus oocytes) and in vitro (in Xenopus oocyte extracts); (iii) the effect of selenium on the Sec tRNA population in various rat tissues following replenishment of extremely selenium deficient rats with this element; and (iv) the biosynthesis of the modified bases on Sec tRNA in Xenopus oocytes展开更多
Codon nonsense mutations include amber, ochre, or opal mutations according to termination codon consisting of three types (TAG, TAA and TGA). Codon nonsense mutations are also divided into natural and artificial mutat...Codon nonsense mutations include amber, ochre, or opal mutations according to termination codon consisting of three types (TAG, TAA and TGA). Codon nonsense mutations are also divided into natural and artificial mutations. We discussed the interaction of codon nonsense mutations and suppressor tRNAs in vitro and in vivo. Nonsense suppressions do not only happen in prokaryotes but also in eukaryotes. Meanwhile, the misreading of termination codon and in-corporation of nonnatural amino acids into proteins are also introduced.展开更多
Using purified bovine liver tRNA￣(Ile) and yeast tRNA￣(Phe), we studied the effects of spermine on the melting curve and melting temperature(Tm) of the tRNAs. The results showed that the absorbance at 260 nm of tRNA...Using purified bovine liver tRNA￣(Ile) and yeast tRNA￣(Phe), we studied the effects of spermine on the melting curve and melting temperature(Tm) of the tRNAs. The results showed that the absorbance at 260 nm of tRNAs decreases with the increase of temperature in the presence of 2 mmol/L spermine. We called this phenomenon hypochromism and reverse-Tm of the tRNAs. It is suggested that spermine binds to tRNAs and stabilizes the secondary structure of the tRNAs.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(m^(1)G9)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
tRNase Z （TRZ） is a ubiquitous endonuclease that removes the 3＇-trailer from precursor tRNAs during maturation. In yeast and animals, TRZ regulates the cell cycle via its （t）RNA processing activity; however, its ...tRNase Z （TRZ） is a ubiquitous endonuclease that removes the 3＇-trailer from precursor tRNAs during maturation. In yeast and animals, TRZ regulates the cell cycle via its （t）RNA processing activity; however, its physiological function in higher plants has not been well characterized. This study describes the identification of a rice （Oryza sativa） TRZ2 mutant; plants homozygous for the osatrz2 mutation were albinos with deficient chlorophyll content. A microscopic analysis of the mutant plants revealed that the transition of proplastids to chloroplasts was arrested at an early stage, and the number and size of the plastids in callus cells was substantially decreased. A genetic complementation test and an RNA interference analysis confirmed that disruption of OsaTRZ2 was responsible for the mutant phenotype. OsaTRZ2 is expressed in all rice tissues, but is preferentially expressed in leaves, sheathes, and calli. OsaTRZ2 was subcellularly localized in chloroplasts, and displayed tRNA 3＇-end processing activity in both in vitro and in vivo assays. In the osatrz2 mutants, transcription of plastid-encoded and nucleus- encoded RNA polymerases was severely reduced and moderately increased, respectively. These results suggest that the tRNA 3＇ processing activity of OsaTRZ2 contributes to chloroplast biogenesis.展开更多
Evidence is emerging that t RNA-derived fragments(t RFs)are regulatory molecules.Studies of t RFs in plants have been based on conventional small RNA sequencing,and focused on profiling of t RF-5 and t RF-3 species.A ...Evidence is emerging that t RNA-derived fragments(t RFs)are regulatory molecules.Studies of t RFs in plants have been based on conventional small RNA sequencing,and focused on profiling of t RF-5 and t RF-3 species.A more comprehensive and quantitative analysis of the entire t RF population is highly necessary.Here,we employ t RNA-seq and YAMAT-seq,and develop a bioinformatics tool to comprehensively profile the expressions of t RNAs and t RFs in plants.We show that in Arabidopsis,approximately half of t RNA genes are extremely weakly expressed,accounting for only 1%of total t RNA abundance,while~12%of t RNA genes contribute to~80%of t RNA abundance.Our t RNA sequencings in various plants reveal that t RNA expression profiles exhibit a cross-species conserved pattern.By characterizing the composition of a highly heterogeneous t RF population,we show that t RNA halves and previously unnoticed 10–16-nt tiny t RFs represent substantial portions.The highly accumulated 13-nt and 16-nt tiny t RFs in Arabidopsis indicate that tiny t RFs are not random t RNA degradation products.Finally,we provide a user-friendly database for displaying the dynamic spatiotemporal expressions of t RNAs and t RFs in the model plants Arabidopsis and rice.展开更多
Transfer RNAs(tRNAs) hold a central place in protein synthesis by interpreting the genetic information stored in DNA into the amino acid sequence of protein,thus functioning as "adaptor" molecules.In recent ...Transfer RNAs(tRNAs) hold a central place in protein synthesis by interpreting the genetic information stored in DNA into the amino acid sequence of protein,thus functioning as "adaptor" molecules.In recent years,however,various studies have shown that tRNAs have additional functions beyond participating in protein synthesis.When suffering from certain nutritional stresses,tRNAs change the level of aminoacylation to became uncharged,and these uncharged tRNAs act as effector molecules to regulate global gene expression,so that the stressed organism copes with the adverse environmental stresses.In budding yeast and certain mammalian cells,the retrograde movement of mature tRNAs from cytoplasm to nucleus serves as a mechanism for the surveillance system within the nucleus to continue monitoring the integrity of tRNAs.On the other hand,this retrograde action effectively reduces the global protein synthesis level under conditions of nutritional starvation.Quite recently,various publications have shown that tRNAs are not stable molecules in an absolute sense.Under certain physiological or environmental stresses,they are specifically cleaved into fragments of different lengths in the anticodon loop or anticodon left arm.These cleavages are not a meaningless random degradation phenomenon.Instead,a novel class of signal molecules such as tRNA halves or sitRNAs may be produced,which are closely correlated with the modulation of global gene expression.Investigation of the regulatory functions of tRNAs is a frontier,which seeks to reveal the structural and functional diversity of tRNAs as well as their vital functions during the expression of genetic information.展开更多
TRMT1 is an N^2-methylguanosine(m^(2)G)and N^2,N^2-methylguanosine((m^(2))_(2)G)methyltransferase that targets G26 of both cytoplasmic and mitochondrial t RNAs.In higher eukaryotes,most cytoplasmic t RNAs with G26 car...TRMT1 is an N^2-methylguanosine(m^(2)G)and N^2,N^2-methylguanosine((m^(2))_(2)G)methyltransferase that targets G26 of both cytoplasmic and mitochondrial t RNAs.In higher eukaryotes,most cytoplasmic t RNAs with G26 carry(m^(2))_(2)G26,although the majority of mitochondrial G26-containing t RNAs carry m^(2)G26 or G26,suggesting differences in the mechanisms by which TRMT1 catalyzes modification of these t RNAs.Loss-of-function mutations of human TRMT1 result in neurological disorders and completely abrogate t RNA:(m^(2))_(2)G26 formation.However,the mechanism underlying the independent catalytic activity of human TRMT1 and identity of its specific substrate remain elusive,hindering a comprehensive understanding of the pathogenesis of neurological disorders caused by TRMT1 mutations.Here,we showed that human TRMT1 independently catalyzes formation of the t RNA:m^(2)G26 or(m^(2))_(2)G26 modification in a substrate-dependent manner,which explains the distinct distribution of m^(2)G26 and(m^(2))_(2)G26 on cytoplasmic and mitochondrial t RNAs.For human TRMT1-mediated t RNA:(m^(2))_(2)G26 formation,the semi-conserved C11:G24 serves as the determinant,and the U10:A25 or G10:C25 base pair is also required,while the size of the variable loop has no effect.We defined the requirements of this recognition mechanism as the“(m^(2))_(2)G26 criteria”.We found that the(m^(2))_(2)G26 modification occurred in almost all the higher eukaryotic t RNAs conforming to these criteria,suggesting the“(m^(2))_(2)G26 criteria”are applicable to other higher eukaryotic t RNAs.展开更多
目的:探讨抗合成酶综合征(ASS)合并间质性肺病(ILD)患者的临床特征和影像学进展的预后因素。方法:收集111例确诊为ASS-ILD的住院患者的人口学、临床资料、血清学指标、影像学资料及肺功能的表现。随访1年内(至少半年),根据高分辨率CT (H...目的:探讨抗合成酶综合征(ASS)合并间质性肺病(ILD)患者的临床特征和影像学进展的预后因素。方法:收集111例确诊为ASS-ILD的住院患者的人口学、临床资料、血清学指标、影像学资料及肺功能的表现。随访1年内(至少半年),根据高分辨率CT (HRCT)影像学的变化分为三组:好转组,稳定组和恶化组。采用χ2检验、Fisher确切概率法比较不同抗氨酰tRNA合成酶(ARS)抗体阳性的ASS-ILD患者临床特征的差异,应用单变量Logistic回归分析评估影像学变化的相关性因素。结果:① 111例ASS-ILD患者中,70名抗Jo-1抗体阳性,17名抗PL-7抗体阳性,15名抗EJ抗体阳性,9名抗PL-12抗体阳性。高雪氏疹是ASS-ILD患者皮肤病变中最常见表现。ASS-ILD最常见的首发症状是呼吸困难。关节炎是抗Jo-1抗体阳性组中最常见的首发症状。抗PL-12抗体阳性组呼吸困难显著高于其他亚组(P = 0.024)。抗PL-12和抗EJ抗体组以咳嗽作为首发症状的发生率显著高于其他亚组(P = 0.000)。② 不同亚组ASS-ILD患者的血清学特征比较,治疗前基线数据显示,抗PL-7和抗PL-12抗体亚组的CD16 + CD56 + (NK)细胞数量显著减少,具有统计学差异(P P P = 0.075)。④ 影像学进展方面,恶化组ASS-ILD患者B淋巴细胞初始数量显著增加,好转组患者糖皮质激素初始剂量更高。统计数据显示CD3-CD19+细胞初始数量(OR = 1.0013, P = 0.014)和初始糖皮质激素用量(OR = 0.9603, P = 0.04)与ILD影像学转归相关。结论:不同抗合成酶抗体亚型的ASS-ILD患者的临床特征不同。B淋巴细胞水平的增加及早期高剂量糖皮质激素强化治疗可能是ASS-ILD患者影像学恶化的独立危险因素。早期高剂量糖皮质激素的强化治疗可能有效改善ILD的影像学预后。Objective: Exploring the clinical characteristics and prognostic factors of imaging progression in patients with antisynthetase syndrome (ASS) complicated with interstitial lung disease (ILD). Methods: Collect demographic, clinical, serological, imaging, and pulmonary function data of 111 hospitalized patients diagnosed with ASS-ILD. Within one year (at least six months) of follow-up, patients were divided into three groups based on changes in high-resolution CT (HRCT) imaging: improvement group, stable group, and deterioration group. Using chi square test and Fisher’s exact probability method to compare the differences in clinical characteristics of ASS-ILD patients with different levels of anti aminoacyl tRNA synthetase (ARS) antibody positivity, and applying univariate cumulative logistic regression analysis to evaluate the correlation factors of imaging changes. Results: ① Among 111 ASS-ILD patients, 70 were positive for anti-Jo-1 antibodies, 17 were positive for anti-PL-7 antibodies, 15 were positive for anti-EJ antibodies, and 9 were positive for anti-PL-12 antibodies. Gottron papules is the most common manifestation of skin lesions in ASS-ILD patients. The most common initial symptom in ASS-ILD patients is dyspnea. Arthritis is the most common initial symptom in the anti-Jo-1 antibody positive group. The respiratory distress in the anti-PL-12 antibody positive group was significantly higher than that in other subgroups (P = 0.024). The incidence of cough as the initial symptom was significantly higher in the anti-PL-12 and anti-EJ antibody groups than in other subgroups (P = 0.000). ② Comparison of serological characteristics among different subgroups of ASS-ILD patients. Baseline data before treatment showed a significant decrease in the number of CD16 + CD56 + (NK) cells in the anti-PL-7 and anti-PL-12 antibody subgroups, with statistical differences (P P P = 0.075). ④ In terms of imaging progress, the initial number of CD3-CD19+cells significantly increased in the worsening group of ASS-ILD patients, while the initial dose of glucocorticoids was higher in the improving group of patients. Statistical data shows that the initial number of B lymphocyte cells (OR = 1.0013, P = 0.014) and the initial dosage of glucocorticoids (OR = 0.9603, P = 0.04) are correlated with the imaging outcome of ILD. Conclusions: The clinical characteristics of ASS-ILD patients with different subtypes of antisynthetase antibodies are different. The increase in B lymphocyte cell levels and early high-dose glucocorticoid enhanced therapy may be independent risk factors for imaging deterioration in ASS-ILD patients. Early high-dose glucocorticoid enhanced therapy may effectively improve the imaging prognosis of ILD.展开更多
转运核糖核酸(tRNA)衍生的小分子RNA(transfer-RNA derived small RNA,tsRNA)是近年来新发现的一类由成熟tRNA或其前体通过特殊的内切酶介导产生的非编码RNA。已有的研究揭示,tsRNA能够在转录及转录后水平上调控基因表达,能以表观遗传...转运核糖核酸(tRNA)衍生的小分子RNA(transfer-RNA derived small RNA,tsRNA)是近年来新发现的一类由成熟tRNA或其前体通过特殊的内切酶介导产生的非编码RNA。已有的研究揭示,tsRNA能够在转录及转录后水平上调控基因表达,能以表观遗传调控因子方式,在多种生物体的生理和病理过程中发挥重要作用,因此,其逐渐成为生物医学的研究热点而引起广泛关注。而且越来越多的证据显示,tsRNA通过对应激反应、细胞增殖与凋亡、神经发育、突触可塑性、神经炎症与免疫调节、表观遗传、RNA加工和蛋白质翻译调控等参与许多神经精神疾病的发生和发展过程。该文主要就tsRNA的生成和分类及其生物学功能,阐述tsRNA在神经发育和神经精神疾病中的作用和可能作用机制,从而进一步揭示tsRNA作为神经精神疾病可靠生物标志物和治疗靶点的潜力。展开更多
消化系统恶性肿瘤是一类由多因素影响的疾病,发病率和病死率均较高,致病机制尚不明确。转运RNA衍生的小RNA(tRNA-derived small RNA,tsRNA)作为一种新型的非编码小RNA受到广泛关注。根据tRNA上核酸酶切割位点的差异,tsRNA可分为tRNA半...消化系统恶性肿瘤是一类由多因素影响的疾病,发病率和病死率均较高,致病机制尚不明确。转运RNA衍生的小RNA(tRNA-derived small RNA,tsRNA)作为一种新型的非编码小RNA受到广泛关注。根据tRNA上核酸酶切割位点的差异,tsRNA可分为tRNA半分子和tRNA衍生片段。大量研究已证实,tsRNA可通过调节靶基因或信号通路参与癌症的各种生物学过程。此外,tsRNA分布广泛、表达稳定,在肿瘤诊断和预后方面具有广阔的应用前景。本文介绍了tsRNA的起源和分类,总结了tsRNA在消化系统恶性肿瘤中的信号通路调控机制和功能失调作用,重点探讨了tsRNA作为消化系统恶性肿瘤诊断和预后生物标志物的临床前景,为将来相关癌症研究提供新思路。展开更多
文摘Selenocysteine (Sec) tRNAs serve as carrier molecules for the biosynthesis of Sec from serine and to donate Sec to protein in response to specific UGA codons. In this study, we describe the current status of Sec tRNAs in higher animals and further we exarnine: (i) the Sec tRNA population in Drosophila; (ii) transcription of the Sec tRNA in vivo (in Xenopus oocytes) and in vitro (in Xenopus oocyte extracts); (iii) the effect of selenium on the Sec tRNA population in various rat tissues following replenishment of extremely selenium deficient rats with this element; and (iv) the biosynthesis of the modified bases on Sec tRNA in Xenopus oocytes
文摘Codon nonsense mutations include amber, ochre, or opal mutations according to termination codon consisting of three types (TAG, TAA and TGA). Codon nonsense mutations are also divided into natural and artificial mutations. We discussed the interaction of codon nonsense mutations and suppressor tRNAs in vitro and in vivo. Nonsense suppressions do not only happen in prokaryotes but also in eukaryotes. Meanwhile, the misreading of termination codon and in-corporation of nonnatural amino acids into proteins are also introduced.
文摘Using purified bovine liver tRNA￣(Ile) and yeast tRNA￣(Phe), we studied the effects of spermine on the melting curve and melting temperature(Tm) of the tRNAs. The results showed that the absorbance at 260 nm of tRNAs decreases with the increase of temperature in the presence of 2 mmol/L spermine. We called this phenomenon hypochromism and reverse-Tm of the tRNAs. It is suggested that spermine binds to tRNAs and stabilizes the secondary structure of the tRNAs.
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(m^(1)G9)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).
基金supported by the 863 Project (2012AA10A303)the Fundamental Research Funds for the Central Universities (2013PY020 and 2013PY062)
文摘tRNase Z （TRZ） is a ubiquitous endonuclease that removes the 3＇-trailer from precursor tRNAs during maturation. In yeast and animals, TRZ regulates the cell cycle via its （t）RNA processing activity; however, its physiological function in higher plants has not been well characterized. This study describes the identification of a rice （Oryza sativa） TRZ2 mutant; plants homozygous for the osatrz2 mutation were albinos with deficient chlorophyll content. A microscopic analysis of the mutant plants revealed that the transition of proplastids to chloroplasts was arrested at an early stage, and the number and size of the plastids in callus cells was substantially decreased. A genetic complementation test and an RNA interference analysis confirmed that disruption of OsaTRZ2 was responsible for the mutant phenotype. OsaTRZ2 is expressed in all rice tissues, but is preferentially expressed in leaves, sheathes, and calli. OsaTRZ2 was subcellularly localized in chloroplasts, and displayed tRNA 3＇-end processing activity in both in vitro and in vivo assays. In the osatrz2 mutants, transcription of plastid-encoded and nucleus- encoded RNA polymerases was severely reduced and moderately increased, respectively. These results suggest that the tRNA 3＇ processing activity of OsaTRZ2 contributes to chloroplast biogenesis.
基金supported by the National Natural Science Foundation of China(31871321,31788103,31770874)Tianjin Natural Science Foundation of China(16JCZDJC33400)Tianjin Rice Industrial Technology System of China(ITTRRS2018006)。
文摘Evidence is emerging that t RNA-derived fragments(t RFs)are regulatory molecules.Studies of t RFs in plants have been based on conventional small RNA sequencing,and focused on profiling of t RF-5 and t RF-3 species.A more comprehensive and quantitative analysis of the entire t RF population is highly necessary.Here,we employ t RNA-seq and YAMAT-seq,and develop a bioinformatics tool to comprehensively profile the expressions of t RNAs and t RFs in plants.We show that in Arabidopsis,approximately half of t RNA genes are extremely weakly expressed,accounting for only 1%of total t RNA abundance,while~12%of t RNA genes contribute to~80%of t RNA abundance.Our t RNA sequencings in various plants reveal that t RNA expression profiles exhibit a cross-species conserved pattern.By characterizing the composition of a highly heterogeneous t RF population,we show that t RNA halves and previously unnoticed 10–16-nt tiny t RFs represent substantial portions.The highly accumulated 13-nt and 16-nt tiny t RFs in Arabidopsis indicate that tiny t RFs are not random t RNA degradation products.Finally,we provide a user-friendly database for displaying the dynamic spatiotemporal expressions of t RNAs and t RFs in the model plants Arabidopsis and rice.
基金Supported by National Natural Science Foundation of China (Grant Nos.30870530 and 30570398)the National Key Basic Research Program of China (Grant No.2005CB724600)
文摘Transfer RNAs(tRNAs) hold a central place in protein synthesis by interpreting the genetic information stored in DNA into the amino acid sequence of protein,thus functioning as "adaptor" molecules.In recent years,however,various studies have shown that tRNAs have additional functions beyond participating in protein synthesis.When suffering from certain nutritional stresses,tRNAs change the level of aminoacylation to became uncharged,and these uncharged tRNAs act as effector molecules to regulate global gene expression,so that the stressed organism copes with the adverse environmental stresses.In budding yeast and certain mammalian cells,the retrograde movement of mature tRNAs from cytoplasm to nucleus serves as a mechanism for the surveillance system within the nucleus to continue monitoring the integrity of tRNAs.On the other hand,this retrograde action effectively reduces the global protein synthesis level under conditions of nutritional starvation.Quite recently,various publications have shown that tRNAs are not stable molecules in an absolute sense.Under certain physiological or environmental stresses,they are specifically cleaved into fragments of different lengths in the anticodon loop or anticodon left arm.These cleavages are not a meaningless random degradation phenomenon.Instead,a novel class of signal molecules such as tRNA halves or sitRNAs may be produced,which are closely correlated with the modulation of global gene expression.Investigation of the regulatory functions of tRNAs is a frontier,which seeks to reveal the structural and functional diversity of tRNAs as well as their vital functions during the expression of genetic information.
基金the National Key Research and Development Program of China(2021YFA1100800,2020YFA0803401)the National Natural Science Foundation of China(32022040,91940302,31971230,31870811,32000919)Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at Shanghai Tech University。
文摘TRMT1 is an N^2-methylguanosine(m^(2)G)and N^2,N^2-methylguanosine((m^(2))_(2)G)methyltransferase that targets G26 of both cytoplasmic and mitochondrial t RNAs.In higher eukaryotes,most cytoplasmic t RNAs with G26 carry(m^(2))_(2)G26,although the majority of mitochondrial G26-containing t RNAs carry m^(2)G26 or G26,suggesting differences in the mechanisms by which TRMT1 catalyzes modification of these t RNAs.Loss-of-function mutations of human TRMT1 result in neurological disorders and completely abrogate t RNA:(m^(2))_(2)G26 formation.However,the mechanism underlying the independent catalytic activity of human TRMT1 and identity of its specific substrate remain elusive,hindering a comprehensive understanding of the pathogenesis of neurological disorders caused by TRMT1 mutations.Here,we showed that human TRMT1 independently catalyzes formation of the t RNA:m^(2)G26 or(m^(2))_(2)G26 modification in a substrate-dependent manner,which explains the distinct distribution of m^(2)G26 and(m^(2))_(2)G26 on cytoplasmic and mitochondrial t RNAs.For human TRMT1-mediated t RNA:(m^(2))_(2)G26 formation,the semi-conserved C11:G24 serves as the determinant,and the U10:A25 or G10:C25 base pair is also required,while the size of the variable loop has no effect.We defined the requirements of this recognition mechanism as the“(m^(2))_(2)G26 criteria”.We found that the(m^(2))_(2)G26 modification occurred in almost all the higher eukaryotic t RNAs conforming to these criteria,suggesting the“(m^(2))_(2)G26 criteria”are applicable to other higher eukaryotic t RNAs.
文摘目的:探讨抗合成酶综合征(ASS)合并间质性肺病(ILD)患者的临床特征和影像学进展的预后因素。方法:收集111例确诊为ASS-ILD的住院患者的人口学、临床资料、血清学指标、影像学资料及肺功能的表现。随访1年内(至少半年),根据高分辨率CT (HRCT)影像学的变化分为三组:好转组,稳定组和恶化组。采用χ2检验、Fisher确切概率法比较不同抗氨酰tRNA合成酶(ARS)抗体阳性的ASS-ILD患者临床特征的差异,应用单变量Logistic回归分析评估影像学变化的相关性因素。结果:① 111例ASS-ILD患者中,70名抗Jo-1抗体阳性,17名抗PL-7抗体阳性,15名抗EJ抗体阳性,9名抗PL-12抗体阳性。高雪氏疹是ASS-ILD患者皮肤病变中最常见表现。ASS-ILD最常见的首发症状是呼吸困难。关节炎是抗Jo-1抗体阳性组中最常见的首发症状。抗PL-12抗体阳性组呼吸困难显著高于其他亚组(P = 0.024)。抗PL-12和抗EJ抗体组以咳嗽作为首发症状的发生率显著高于其他亚组(P = 0.000)。② 不同亚组ASS-ILD患者的血清学特征比较,治疗前基线数据显示,抗PL-7和抗PL-12抗体亚组的CD16 + CD56 + (NK)细胞数量显著减少,具有统计学差异(P P P = 0.075)。④ 影像学进展方面,恶化组ASS-ILD患者B淋巴细胞初始数量显著增加,好转组患者糖皮质激素初始剂量更高。统计数据显示CD3-CD19+细胞初始数量(OR = 1.0013, P = 0.014)和初始糖皮质激素用量(OR = 0.9603, P = 0.04)与ILD影像学转归相关。结论:不同抗合成酶抗体亚型的ASS-ILD患者的临床特征不同。B淋巴细胞水平的增加及早期高剂量糖皮质激素强化治疗可能是ASS-ILD患者影像学恶化的独立危险因素。早期高剂量糖皮质激素的强化治疗可能有效改善ILD的影像学预后。Objective: Exploring the clinical characteristics and prognostic factors of imaging progression in patients with antisynthetase syndrome (ASS) complicated with interstitial lung disease (ILD). Methods: Collect demographic, clinical, serological, imaging, and pulmonary function data of 111 hospitalized patients diagnosed with ASS-ILD. Within one year (at least six months) of follow-up, patients were divided into three groups based on changes in high-resolution CT (HRCT) imaging: improvement group, stable group, and deterioration group. Using chi square test and Fisher’s exact probability method to compare the differences in clinical characteristics of ASS-ILD patients with different levels of anti aminoacyl tRNA synthetase (ARS) antibody positivity, and applying univariate cumulative logistic regression analysis to evaluate the correlation factors of imaging changes. Results: ① Among 111 ASS-ILD patients, 70 were positive for anti-Jo-1 antibodies, 17 were positive for anti-PL-7 antibodies, 15 were positive for anti-EJ antibodies, and 9 were positive for anti-PL-12 antibodies. Gottron papules is the most common manifestation of skin lesions in ASS-ILD patients. The most common initial symptom in ASS-ILD patients is dyspnea. Arthritis is the most common initial symptom in the anti-Jo-1 antibody positive group. The respiratory distress in the anti-PL-12 antibody positive group was significantly higher than that in other subgroups (P = 0.024). The incidence of cough as the initial symptom was significantly higher in the anti-PL-12 and anti-EJ antibody groups than in other subgroups (P = 0.000). ② Comparison of serological characteristics among different subgroups of ASS-ILD patients. Baseline data before treatment showed a significant decrease in the number of CD16 + CD56 + (NK) cells in the anti-PL-7 and anti-PL-12 antibody subgroups, with statistical differences (P P P = 0.075). ④ In terms of imaging progress, the initial number of CD3-CD19+cells significantly increased in the worsening group of ASS-ILD patients, while the initial dose of glucocorticoids was higher in the improving group of patients. Statistical data shows that the initial number of B lymphocyte cells (OR = 1.0013, P = 0.014) and the initial dosage of glucocorticoids (OR = 0.9603, P = 0.04) are correlated with the imaging outcome of ILD. Conclusions: The clinical characteristics of ASS-ILD patients with different subtypes of antisynthetase antibodies are different. The increase in B lymphocyte cell levels and early high-dose glucocorticoid enhanced therapy may be independent risk factors for imaging deterioration in ASS-ILD patients. Early high-dose glucocorticoid enhanced therapy may effectively improve the imaging prognosis of ILD.
文摘转运核糖核酸(tRNA)衍生的小分子RNA(transfer-RNA derived small RNA,tsRNA)是近年来新发现的一类由成熟tRNA或其前体通过特殊的内切酶介导产生的非编码RNA。已有的研究揭示,tsRNA能够在转录及转录后水平上调控基因表达,能以表观遗传调控因子方式,在多种生物体的生理和病理过程中发挥重要作用,因此,其逐渐成为生物医学的研究热点而引起广泛关注。而且越来越多的证据显示,tsRNA通过对应激反应、细胞增殖与凋亡、神经发育、突触可塑性、神经炎症与免疫调节、表观遗传、RNA加工和蛋白质翻译调控等参与许多神经精神疾病的发生和发展过程。该文主要就tsRNA的生成和分类及其生物学功能,阐述tsRNA在神经发育和神经精神疾病中的作用和可能作用机制,从而进一步揭示tsRNA作为神经精神疾病可靠生物标志物和治疗靶点的潜力。
文摘消化系统恶性肿瘤是一类由多因素影响的疾病,发病率和病死率均较高,致病机制尚不明确。转运RNA衍生的小RNA(tRNA-derived small RNA,tsRNA)作为一种新型的非编码小RNA受到广泛关注。根据tRNA上核酸酶切割位点的差异,tsRNA可分为tRNA半分子和tRNA衍生片段。大量研究已证实,tsRNA可通过调节靶基因或信号通路参与癌症的各种生物学过程。此外,tsRNA分布广泛、表达稳定,在肿瘤诊断和预后方面具有广阔的应用前景。本文介绍了tsRNA的起源和分类,总结了tsRNA在消化系统恶性肿瘤中的信号通路调控机制和功能失调作用,重点探讨了tsRNA作为消化系统恶性肿瘤诊断和预后生物标志物的临床前景,为将来相关癌症研究提供新思路。
