In eukaryotic cells,both alternative splicing and alternative polyadenylation(APA)play essential roles in the gene regulation network.U1 small ribonucleoprotein particle(U1 snRNP)is a major component of spliceosome,an...In eukaryotic cells,both alternative splicing and alternative polyadenylation(APA)play essential roles in the gene regulation network.U1 small ribonucleoprotein particle(U1 snRNP)is a major component of spliceosome,and U1 snRNP complex can suppress proximal APA sites through crosstalking with 3end processing factors.However,here we show that both knockdown and overexpression of SNRPA,SNRPC,SNRNP70,and SNRPD2,the U1 snRNP proteins,promote the usage of proximal APA sites at the transcriptome level.SNRNP70 can drive the phase transition of PABPN1 from droplet to aggregate,which may reduce the repressive effects of PABPN1 on the proximal APA sites.Additionally,SNRNP70 can also promote the proximal APA sites by recruiting CPSF6,suggesting that the function of CPSF6 on APA is related with other RNA-binding proteins and cell context-dependent.Consequently,these results reveal that,on the contrary to U1 snRNP complex,the free proteins of U1 snRNP complex can promote proximal APA sites through the interaction with 3end processing machinery.展开更多
There are multiple reports of autoimmune response in patients with lung cancer. To investigate whether a novel autoantibody is present in patients with lung cancer and evaluate its clinical diagnostic and prognostic v...There are multiple reports of autoimmune response in patients with lung cancer. To investigate whether a novel autoantibody is present in patients with lung cancer and evaluate its clinical diagnostic and prognostic value, sera from 10 patients with lung cancer and 10 normal individuals were analyzed using immunofluorescence and Western blotting. It was found that one serum sample from the patients with squamous carcinoma gave a fine speckled pattern staining in nucleus and had a high titer antinuclear autoantibody which could recognize 31 kD of nuclear protein isolated from both cancer cells and normal cells. The same patient’s serum was further used to immunoprecipitate the target antigen. The protein bands were excised from the SDS-PAGE gels and were analyzed with a Qstar Pulser I Quadrupole time-flight mass spec-trometer, and the 31 kD target antigen was identified as U1-A snRNP. To test the prevalence of anti-U1-A snRNP antibody, sera from 93 patients including 36 squmaous carcinomas (SCC), 26 adenocarcinomas (Ad), and 31 small cell carcinomas (SCLC) were screened by Western blotting. The results demonstrated that anti-U1-A snRNP antibody was present in 50% of SCC sera, 26.9% of Ad sera and 54.8% of SCLC sera. In this paper, we report for the first time that anti-U1-A snRNP antibody could be detected in the patients with lung cancer.展开更多
脊髓性肌萎缩症（spinal muscular atrophy，SMA）是一类与运动神经元存活基因（survival of motor neurons gene，SMN gene）突变有关的神经系统变性疾病，而SMN基因的转录产物即为SMN蛋白（survival of motorneurons protein，SMN pro...脊髓性肌萎缩症（spinal muscular atrophy，SMA）是一类与运动神经元存活基因（survival of motor neurons gene，SMN gene）突变有关的神经系统变性疾病，而SMN基因的转录产物即为SMN蛋白（survival of motorneurons protein，SMN protein）。SMN蛋白与多种蛋白结合后发挥作用，如SMN-Sm蛋白的相互作用在富含尿嘧啶的小核核糖核蛋白体（uridine—richsmallribonucleo—proteins，UsnRNPs）转运装配中有重要意义。SMN蛋白是通过其Tudor结构域与剪接体sm蛋白的二甲基化修饰的富含精氨酸一氨基乙酸域（ar—ginineandglycine—rich，RG）结合。展开更多
Spliceosomal RNAs are a family of small nuclear RNAs(snRNAs)that are essential for pre-mRNA splicing.All vertebrate spliceosomal snRNAs are extensively pseudouridylated after transcription.Pseudouridines in spliceosom...Spliceosomal RNAs are a family of small nuclear RNAs(snRNAs)that are essential for pre-mRNA splicing.All vertebrate spliceosomal snRNAs are extensively pseudouridylated after transcription.Pseudouridines in spliceosomal snRNAs are generally clustered in regions that are functionally important during splicing.Many of these modified nucleotides are conserved across species lines.Recent studies have demonstrated that spliceosomal snRNA pseudouridylation is catalyzed by two different mechanisms:an RNA-dependent mechanism and an RNA-independent mechanism.The functions of the pseudouridines in spliceosomal snRNAs(U2 snRNA in particular)have also been extensively studied.Experimental data indicate that virtually all pseudouridines in U2 snRNA are functionally important.Besides the currently known pseudouridines(constitutive modifications),recent work has also indicated that pseudouridylation can be induced at novel positions under stress conditions,thus strongly suggesting that pseudouridylation is also a regulatory modification.展开更多
U1 small nuclear ribonucleoproteins(U1 snRNP)associates with 5ʹsplice sites in the form of ribonucleoprotein particles and is highly conserved among species.The physiological functions of U1 snRNP in a lepidopteran mo...U1 small nuclear ribonucleoproteins(U1 snRNP)associates with 5ʹsplice sites in the form of ribonucleoprotein particles and is highly conserved among species.The physiological functions of U1 snRNP in a lepidopteran model insect Bombyx mori is mostly unknown.Here,we showed that U1 snRNP plays an important role in the development of silkworm.Knockout of U1 snRNP in silkworm showed either delayed or stationary 1st instar larva development compared with the wild-type group.U1 snRNP deletion mutants exhibited abnormal cellular phenotypes with enlarged cell nucleus,scant cytoplasm and enlarged nuclei.RNA-seq analysis revealed that genes involved in metabolic pathway,biosynthesis of secondary metabolites and steroid hormone biosynthesis were significantly affected by U1 snRNP depletion.Taken together,our study suggests that U1 snRNP homeostasis plays an important role in silkworm development.展开更多
基金supported by the National Natural Science Foundation of China(31971332 to Y.F.,91942301 and 81430099 to A.X,and 32000450 to L.C.).
文摘In eukaryotic cells,both alternative splicing and alternative polyadenylation(APA)play essential roles in the gene regulation network.U1 small ribonucleoprotein particle(U1 snRNP)is a major component of spliceosome,and U1 snRNP complex can suppress proximal APA sites through crosstalking with 3end processing factors.However,here we show that both knockdown and overexpression of SNRPA,SNRPC,SNRNP70,and SNRPD2,the U1 snRNP proteins,promote the usage of proximal APA sites at the transcriptome level.SNRNP70 can drive the phase transition of PABPN1 from droplet to aggregate,which may reduce the repressive effects of PABPN1 on the proximal APA sites.Additionally,SNRNP70 can also promote the proximal APA sites by recruiting CPSF6,suggesting that the function of CPSF6 on APA is related with other RNA-binding proteins and cell context-dependent.Consequently,these results reveal that,on the contrary to U1 snRNP complex,the free proteins of U1 snRNP complex can promote proximal APA sites through the interaction with 3end processing machinery.
基金This work was supported by the National Natural Science Foundation of China(Grant No.30370712)863 Project(Grant No.2002AA232031).
文摘There are multiple reports of autoimmune response in patients with lung cancer. To investigate whether a novel autoantibody is present in patients with lung cancer and evaluate its clinical diagnostic and prognostic value, sera from 10 patients with lung cancer and 10 normal individuals were analyzed using immunofluorescence and Western blotting. It was found that one serum sample from the patients with squamous carcinoma gave a fine speckled pattern staining in nucleus and had a high titer antinuclear autoantibody which could recognize 31 kD of nuclear protein isolated from both cancer cells and normal cells. The same patient’s serum was further used to immunoprecipitate the target antigen. The protein bands were excised from the SDS-PAGE gels and were analyzed with a Qstar Pulser I Quadrupole time-flight mass spec-trometer, and the 31 kD target antigen was identified as U1-A snRNP. To test the prevalence of anti-U1-A snRNP antibody, sera from 93 patients including 36 squmaous carcinomas (SCC), 26 adenocarcinomas (Ad), and 31 small cell carcinomas (SCLC) were screened by Western blotting. The results demonstrated that anti-U1-A snRNP antibody was present in 50% of SCC sera, 26.9% of Ad sera and 54.8% of SCLC sera. In this paper, we report for the first time that anti-U1-A snRNP antibody could be detected in the patients with lung cancer.
文摘脊髓性肌萎缩症（spinal muscular atrophy，SMA）是一类与运动神经元存活基因（survival of motor neurons gene，SMN gene）突变有关的神经系统变性疾病，而SMN基因的转录产物即为SMN蛋白（survival of motorneurons protein，SMN protein）。SMN蛋白与多种蛋白结合后发挥作用，如SMN-Sm蛋白的相互作用在富含尿嘧啶的小核核糖核蛋白体（uridine—richsmallribonucleo—proteins，UsnRNPs）转运装配中有重要意义。SMN蛋白是通过其Tudor结构域与剪接体sm蛋白的二甲基化修饰的富含精氨酸一氨基乙酸域（ar—ginineandglycine—rich，RG）结合。
文摘Spliceosomal RNAs are a family of small nuclear RNAs(snRNAs)that are essential for pre-mRNA splicing.All vertebrate spliceosomal snRNAs are extensively pseudouridylated after transcription.Pseudouridines in spliceosomal snRNAs are generally clustered in regions that are functionally important during splicing.Many of these modified nucleotides are conserved across species lines.Recent studies have demonstrated that spliceosomal snRNA pseudouridylation is catalyzed by two different mechanisms:an RNA-dependent mechanism and an RNA-independent mechanism.The functions of the pseudouridines in spliceosomal snRNAs(U2 snRNA in particular)have also been extensively studied.Experimental data indicate that virtually all pseudouridines in U2 snRNA are functionally important.Besides the currently known pseudouridines(constitutive modifications),recent work has also indicated that pseudouridylation can be induced at novel positions under stress conditions,thus strongly suggesting that pseudouridylation is also a regulatory modification.
基金supported by grants from the National Science Foundation of China(31830093,32021001 and 31802005)Strategic Priority Research Program of Chinese Academy of Sciences(XDB11010600).
文摘U1 small nuclear ribonucleoproteins(U1 snRNP)associates with 5ʹsplice sites in the form of ribonucleoprotein particles and is highly conserved among species.The physiological functions of U1 snRNP in a lepidopteran model insect Bombyx mori is mostly unknown.Here,we showed that U1 snRNP plays an important role in the development of silkworm.Knockout of U1 snRNP in silkworm showed either delayed or stationary 1st instar larva development compared with the wild-type group.U1 snRNP deletion mutants exhibited abnormal cellular phenotypes with enlarged cell nucleus,scant cytoplasm and enlarged nuclei.RNA-seq analysis revealed that genes involved in metabolic pathway,biosynthesis of secondary metabolites and steroid hormone biosynthesis were significantly affected by U1 snRNP depletion.Taken together,our study suggests that U1 snRNP homeostasis plays an important role in silkworm development.
