The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Qiang Zhou - One of the best experts on this subject based on the ideXlab platform.
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the 7sk Small Nuclear RNA inhibits the cdk9 cyclin t1 kinase to control transcription
Nature, 2001Co-Authors: Zhiyuan Yang, Qiang ZhouAbstract:The human positive transcription elongation factor P-TEFb, consisting of a CDK9/cyclin T1 heterodimer, functions as both a general and an HIV-1 Tat-specific transcription factor1,2. P-TEFb activates transcription by phosphorylating RNA polymerase (Pol) II, leading to the formation of processive elongation complexes. As a Tat cofactor, P-TEFb stimulates HIV-1 transcription by interacting with Tat and the transactivating responsive (TAR) RNA structure located at the 5′ end of the nascent viral transcript3. Here we identified 7SK, an abundant and evolutionarily conserved Small Nuclear RNA (snRNA) of unknown function4,5, as a specific P-TEFb-associated factor. 7SK inhibits general and HIV-1 Tat-specific transcriptional activities of P-TEFb in vivo and in vitro by inhibiting the kinase activity of CDK9 and preventing recruitment of P-TEFb to the HIV-1 promoter. 7SK is efficiently dissociated from P-TEFb by treatment of cells with ultraviolet irradiation and actinomycin D. As these two agents have been shown to significantly enhance HIV-1 transcription and phosphorylation of Pol II (refs 6,7,8), our data provide a mechanistic explanation for their stimulatory effects. The 7SK/P-TEFb interaction may serve as a principal control point for the induction of cellular and HIV-1 viral gene expression during stress-related responses. Our studies demonstrate the involvement of an snRNA in controlling the activity of a Cdk–cyclin kinase.
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The 7SK Small Nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription
Nature, 2001Co-Authors: Zhiyuan Yang, Qingwei Zhu, Kunxin Luo, Qiang ZhouAbstract:The human positive transcription elongation factor P-TEFb, consisting of a CDK9/cyclin T1 heterodimer, functions as both a general and an HIV-1 Tat-specific transcription factor1,2. P-TEFb activates transcription by phosphorylating RNA polymerase (Pol) II, leading to the formation of processive elongation complexes. As a Tat cofactor, P-TEFb stimulates HIV-1 transcription by interacting with Tat and the transactivating responsive (TAR) RNA structure located at the 5′ end of the nascent viral transcript3. Here we identified 7SK, an abundant and evolutionarily conserved Small Nuclear RNA (snRNA) of unknown function4,5, as a specific P-TEFb-associated factor. 7SK inhibits general and HIV-1 Tat-specific transcriptional activities of P-TEFb in vivo and in vitro by inhibiting the kinase activity of CDK9 and preventing recruitment of P-TEFb to the HIV-1 promoter. 7SK is efficiently dissociated from P-TEFb by treatment of cells with ultraviolet irradiation and actinomycin D. As these two agents have been shown to significantly enhance HIV-1 transcription and phosphorylation of Pol II (refs 6,7,8), our data provide a mechanistic explanation for their stimulatory effects. The 7SK/P-TEFb interaction may serve as a principal control point for the induction of cellular and HIV-1 viral gene expression during stress-related responses. Our studies demonstrate the involvement of an snRNA in controlling the activity of a Cdk–cyclin kinase.
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the 7sk Small Nuclear RNA inhibits the cdk9 cyclin t1 kinase to control transcription
Nature, 2001Co-Authors: Zhiyuan Yang, Qingwei Zhu, Kunxin Luo, Qiang ZhouAbstract:The human positive transcription elongation factor P-TEFb, consisting of a CDK9/cyclin T1 heterodimer, functions as both a general and an HIV-1 Tat-specific transcription factor1,2. P-TEFb activates transcription by phosphorylating RNA polymerase (Pol) II, leading to the formation of processive elongation complexes. As a Tat cofactor, P-TEFb stimulates HIV-1 transcription by interacting with Tat and the transactivating responsive (TAR) RNA structure located at the 5′ end of the nascent viral transcript3. Here we identified 7SK, an abundant and evolutionarily conserved Small Nuclear RNA (snRNA) of unknown function4,5, as a specific P-TEFb-associated factor. 7SK inhibits general and HIV-1 Tat-specific transcriptional activities of P-TEFb in vivo and in vitro by inhibiting the kinase activity of CDK9 and preventing recruitment of P-TEFb to the HIV-1 promoter. 7SK is efficiently dissociated from P-TEFb by treatment of cells with ultraviolet irradiation and actinomycin D. As these two agents have been shown to significantly enhance HIV-1 transcription and phosphorylation of Pol II (refs 6,7,8), our data provide a mechanistic explanation for their stimulatory effects. The 7SK/P-TEFb interaction may serve as a principal control point for the induction of cellular and HIV-1 viral gene expression during stress-related responses. Our studies demonstrate the involvement of an snRNA in controlling the activity of a Cdk–cyclin kinase.
Zhiyuan Yang - One of the best experts on this subject based on the ideXlab platform.
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the 7sk Small Nuclear RNA inhibits the cdk9 cyclin t1 kinase to control transcription
Nature, 2001Co-Authors: Zhiyuan Yang, Qiang ZhouAbstract:The human positive transcription elongation factor P-TEFb, consisting of a CDK9/cyclin T1 heterodimer, functions as both a general and an HIV-1 Tat-specific transcription factor1,2. P-TEFb activates transcription by phosphorylating RNA polymerase (Pol) II, leading to the formation of processive elongation complexes. As a Tat cofactor, P-TEFb stimulates HIV-1 transcription by interacting with Tat and the transactivating responsive (TAR) RNA structure located at the 5′ end of the nascent viral transcript3. Here we identified 7SK, an abundant and evolutionarily conserved Small Nuclear RNA (snRNA) of unknown function4,5, as a specific P-TEFb-associated factor. 7SK inhibits general and HIV-1 Tat-specific transcriptional activities of P-TEFb in vivo and in vitro by inhibiting the kinase activity of CDK9 and preventing recruitment of P-TEFb to the HIV-1 promoter. 7SK is efficiently dissociated from P-TEFb by treatment of cells with ultraviolet irradiation and actinomycin D. As these two agents have been shown to significantly enhance HIV-1 transcription and phosphorylation of Pol II (refs 6,7,8), our data provide a mechanistic explanation for their stimulatory effects. The 7SK/P-TEFb interaction may serve as a principal control point for the induction of cellular and HIV-1 viral gene expression during stress-related responses. Our studies demonstrate the involvement of an snRNA in controlling the activity of a Cdk–cyclin kinase.
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The 7SK Small Nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription
Nature, 2001Co-Authors: Zhiyuan Yang, Qingwei Zhu, Kunxin Luo, Qiang ZhouAbstract:The human positive transcription elongation factor P-TEFb, consisting of a CDK9/cyclin T1 heterodimer, functions as both a general and an HIV-1 Tat-specific transcription factor1,2. P-TEFb activates transcription by phosphorylating RNA polymerase (Pol) II, leading to the formation of processive elongation complexes. As a Tat cofactor, P-TEFb stimulates HIV-1 transcription by interacting with Tat and the transactivating responsive (TAR) RNA structure located at the 5′ end of the nascent viral transcript3. Here we identified 7SK, an abundant and evolutionarily conserved Small Nuclear RNA (snRNA) of unknown function4,5, as a specific P-TEFb-associated factor. 7SK inhibits general and HIV-1 Tat-specific transcriptional activities of P-TEFb in vivo and in vitro by inhibiting the kinase activity of CDK9 and preventing recruitment of P-TEFb to the HIV-1 promoter. 7SK is efficiently dissociated from P-TEFb by treatment of cells with ultraviolet irradiation and actinomycin D. As these two agents have been shown to significantly enhance HIV-1 transcription and phosphorylation of Pol II (refs 6,7,8), our data provide a mechanistic explanation for their stimulatory effects. The 7SK/P-TEFb interaction may serve as a principal control point for the induction of cellular and HIV-1 viral gene expression during stress-related responses. Our studies demonstrate the involvement of an snRNA in controlling the activity of a Cdk–cyclin kinase.
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the 7sk Small Nuclear RNA inhibits the cdk9 cyclin t1 kinase to control transcription
Nature, 2001Co-Authors: Zhiyuan Yang, Qingwei Zhu, Kunxin Luo, Qiang ZhouAbstract:The human positive transcription elongation factor P-TEFb, consisting of a CDK9/cyclin T1 heterodimer, functions as both a general and an HIV-1 Tat-specific transcription factor1,2. P-TEFb activates transcription by phosphorylating RNA polymerase (Pol) II, leading to the formation of processive elongation complexes. As a Tat cofactor, P-TEFb stimulates HIV-1 transcription by interacting with Tat and the transactivating responsive (TAR) RNA structure located at the 5′ end of the nascent viral transcript3. Here we identified 7SK, an abundant and evolutionarily conserved Small Nuclear RNA (snRNA) of unknown function4,5, as a specific P-TEFb-associated factor. 7SK inhibits general and HIV-1 Tat-specific transcriptional activities of P-TEFb in vivo and in vitro by inhibiting the kinase activity of CDK9 and preventing recruitment of P-TEFb to the HIV-1 promoter. 7SK is efficiently dissociated from P-TEFb by treatment of cells with ultraviolet irradiation and actinomycin D. As these two agents have been shown to significantly enhance HIV-1 transcription and phosphorylation of Pol II (refs 6,7,8), our data provide a mechanistic explanation for their stimulatory effects. The 7SK/P-TEFb interaction may serve as a principal control point for the induction of cellular and HIV-1 viral gene expression during stress-related responses. Our studies demonstrate the involvement of an snRNA in controlling the activity of a Cdk–cyclin kinase.
Nouria Hernandez - One of the best experts on this subject based on the ideXlab platform.
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Mitotic Functions for SNAP45, a Subunit of the Small Nuclear RNA-activating Protein Complex SNAPc
The Journal of biological chemistry, 2008Co-Authors: Mayilvahanan Shanmugam, Nouria HernandezAbstract:The Small Nuclear RNA-activating protein complex SNAP(c) is required for transcription of Small Nuclear RNA genes and binds to a proximal sequence element in their promoters. SNAP(c) contains five types of subunits stably associated with each other. Here we show that one of these polypeptides, SNAP45, also known as PTF delta, localizes to centrosomes during parts of mitosis, as well as to the spindle midzone during anaphase and the mid-body during telophase. Consistent with localization to these mitotic structures, both down- and up-regulation of SNAP45 lead to a G(2)/M arrest with cells displaying abnormal mitotic structures. In contrast, down-regulation of SNAP190, another SNAP(c) subunit, leads to an accumulation of cells with a G(0)/G(1) DNA content. These results are consistent with the proposal that SNAP45 plays two roles in the cell, one as a subunit of the transcription factor SNAP(c) and another as a factor required for proper mitotic progression.
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Small Nuclear RNA genes a model system to study fundamental mechanisms of transcription
Journal of Biological Chemistry, 2001Co-Authors: Nouria HernandezAbstract:The human Small Nuclear RNA (snRNA)1 genes, which encode snRNAs that are involved in RNA processing reactions such as mRNA splicing, serve as prototypes for a family of genes whose promoters are characterized by the presence of a proximal sequence element (PSE) and a distal sequence element (DSE). From a transcription point of view, this family of genes is highly interesting because all of its members have very similar promoters, even though some of them are transcribed by RNA polymerase (pol) II and others by pol III. As a result, the snRNA genes have served as a model system to explore how RNA polymerase specificity is determined and, in general, to compare the pol II and III transcription machineries. This has led to the concept that the pol II and III transcription machineries use common factors, the best known of which is the TATA box binding protein (TBP). In addition, the relative simplicity of these promoters has also made them an attractive system to study how transcriptional activators perform their function.
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a map of protein protein contacts within the Small Nuclear RNA activating protein complex snapc
Journal of Biological Chemistry, 2001Co-Authors: Nouria HernandezAbstract:Abstract The nucleation of RNA polymerases I–III transcription complexes is usually directed by distinct multisubunit factors. In the case of the human RNA polymerase II and III Small Nuclear RNA (snRNA) genes, whose core promoters consist of a proximal sequence element (PSE) and a PSE combined with a TATA box, respectively, the same multisubunit complex is involved in the establishment of RNA polymerase II and III initiation complexes. This factor, the snRNA-activating protein complex or SNAPc, binds to the PSE of both types of promoters and contains five types of subunits, SNAP190, SNAP50, SNAP45, SNAP43, and SNAP19. SNAPc binds cooperatively with both Oct-1, an activator of snRNA promoters, and in the RNA polymerase III snRNA promoters, with TATA-binding protein, which binds to the TATA box located downstream of the PSE. Here we have defined subunit domains required for SNAPc subunit-subunit association, and we show that complexes containing little more than the domains mapped here as required for subunit-subunit contacts bind specifically to the PSE. These data provide a detailed map of the subunit-subunit interactions within a multifunctional basal transcription complex.
Tokio Tani - One of the best experts on this subject based on the ideXlab platform.
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involvement of the spliceosomal u4 Small Nuclear RNA in heterochromatic gene silencing at fission yeast centromeres
Journal of Biological Chemistry, 2010Co-Authors: Madoka Chinen, Misato Morita, Kazuhiro Fukumura, Tokio TaniAbstract:prp13-1 is one of the mutants isolated in a screen for defective pre-mRNA splicing at a nonpermissive temperature in fission yeast Schizosaccharomyces pombe. We cloned the prp13+ gene and found that it encodes U4 Small Nuclear RNA (snRNA) involved in the assembly of the spliceosome. The prp13-1 mutant produced elongated cells, a phenotype similar to cell division cycle mutants, and displays a high incidence of lagging chromosomes on anaphase spindles. The mutant is hypersensitive to the microtubule-destabilizing drug thiabendazole, supporting that prp13-1 has a defect in chromosomal segregation. We found that the prp13-1 mutation resulted in expression of the ura4+ gene inserted in the pericentromeric heterochromatin region and reduced recruitment of the heterochromatin protein Swi6p to that region, indicating defects in the formation of pericentromeric heterochromatin, which is essential for the segregation of chromosomes, in prp13-1. The formation of centromeric heterochromatin is induced by the RNA interference (RNAi) system in S. pombe. In prp13-1, the processing of centromeric noncoding RNAs to siRNAs, which direct the heterochromatin formation, was impaired and unprocessed noncoding RNAs were accumulated. These results suggest that U4 snRNA is required for the RNAi-directed heterochromatic gene silencing at the centromeres. In relation to the linkage between the spliceosomal U4 snRNA and the RNAi-directed formation of heterochromatin, we identified a mRNA-type intron in the centromeric noncoding RNAs. We propose a model in which the assembly of the spliceosome or a sub-spliceosome complex on the intron-containing centromeric noncoding RNAs facilitates the RNAi-directed formation of heterochromatin at centromeres, through interaction with the RNA-directed RNA polymerase complex.
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Spliceosomal introns in conserved sequences of U1 and U5 Small Nuclear RNA genes in yeast Rhodotorula hasegawae.
Journal of biochemistry, 1996Co-Authors: Yuzi Takahashi, Tokio Tani, Yasumi OhshimaAbstract:U1, U2, U4, U5, and U6 Small Nuclear RNAs are essential for precursor mRNA splicing. We previously found one and four mRNA-type, or spliceosomal introns, in the U2 and U6 genes, respectively, of yeast Rhodotorula hasegawae (Erythrobasidium hasegawianum). We proposed that U2 and U6 RNAs form a catalytic core for precursor mRNA splicing and that the introns in those Small Nuclear RNA genes may have been acquired through reverse splicing of an intron from a precursor mRNA into a catalytic site in Small Nuclear RNAs. In the present study, we analyzed U1, U4, and U5 genes in R. hasegawae. One spliceosomal intron was found in the U1 region forming base-pairs with a 5' splice site of a precursor mRNA. The U5 gene has two spliceosomal introns in the region that interacts with 5' and 3' splice sites. In contrast, the gene for U4 RNA, which is released from the spliceosome prior to the first step of the splicing reaction, has no intron. These results lend a further support to the proposed relation between presence and position of an intron in an Small Nuclear RNA gene and the function of the encoded Small Nuclear RNA.
Alexander Baraniskin - One of the best experts on this subject based on the ideXlab platform.
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circulating u2 Small Nuclear RNA fragments as a novel diagnostic biomarker for primary central nervous system lymphoma
Neuro-oncology, 2016Co-Authors: Alexander Baraniskin, Elena Zaslavska, Stefanie Nopeldunnebacke, Guido Ahle, Sabine Seidel, Uwe Schlegel, Wolff Schmiegel, Stephan A Hahn, Roland SchroersAbstract:BACKGROUND Primary central nervous system lymphomas (PCNSLs) are highly aggressive tumors. Chemotherapy has improved prognosis significantly; however, early diagnosis is crucial for effective treatment. Presently, the diagnosis of PCNSL depends on histopathology of tumor biopsies. We have previously demonstrated differential expression of microRNAs in cerebrospinal fluid (CSF) samples from patients with PCNSL. Based on promising findings about circulating U2 Small Nuclear RNA fragments (RNU2-1f) as novel blood-based biomarkers for pancreatic, colorectal, and lung cancer, we investigated RNU2-1f in the CSF of PCNSL patients. METHODS CSF was collected from patients with PCNSL (n = 72) and control patients with various neurologic disorders (n = 47). Sequential CSF samples were collected from 9 PCNSL patients. RNU2-1f levels were measured by real-time polymerase chain reaction. RESULTS Measurement of RNU2-1f levels in CSF enabled the differentiation of patients with PCNSL from controls with an area under the curve (AUC) of 0.909 with a sensitivity of 68.1% and a specificity of 91.4%. The diagnostic accuracy was further improved by combined determination of RNU2-1f and miR-21, resulting in AUC of 0.987 with a sensitivity of 91.7% and a specificity of 95.7%. In consecutive measurements of RNU2-1f, which were performed in 9 patients at different stages of the disease course, RNU2-1f CSF levels paralleled the course of the disease. CONCLUSIONS Our data suggest that the measurement of RNU2-1f detected in CSF can be used as a diagnostic marker and also as a possible marker for treatment monitoring. These promising results need to be evaluated within a larger patient cohort.
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circulating u2 Small Nuclear RNA fragments as a novel diagnostic tool for patients with epithelial ovarian cancer
Clinical Chemistry, 2014Co-Authors: Jan Dominik Kuhlmann, Alexander Baraniskin, Stephan A Hahn, Frank Mosel, Maren Bredemeier, Pauline Wimberger, Rainer Kimmig, Sabine KasimirbauerAbstract:BACKGROUND: Ovarian cancer is the leading cause of death among malignancies in women. Despite advances in treatment, >50% of patients relapse. For disease monitoring, the identification of a blood-based biomarker would be of prime interest. In this regard, noncoding RNAs, such as microRNA (miRNA) or Small Nuclear RNA (snRNA), have been suggested as biomarkers for noninvasive cancer diagnosis. In the present study, we sought to identify differentially expressed miRNA/snRNA in sera of ovarian cancer patients and investigate their potential to aid in therapy monitoring. METHODS: miRNA/snRNA abundance was investigated in serum (n = 10) by microarray analysis and validated in an extended serum set (n = 119) by reverse-transcription quantitative PCR. RESULTS: Abundance of U2-1 snRNA fragment (RNU2-1f) was significantly increased in sera of ovarian cancer patients ( P < 0.0001) and paralleled InteRNAtional Federation of Gynecology and Obstetrics stage as well as residual tumor burden after surgery ( P < 0.0001 and P = 0.011, respectively). Moreover, for patients with suboptimal debulking, preoperative RNU2-1f concentration was associated with radiographic response after chemotherapy and with platinum resistance ( P = 0.0088 and P = 0.0015, respectively). Interestingly, according to the RNU2-1f abundance dynamics, persistent RNU2-1f positivity before surgery and after chemotherapy identified a subgroup of patients with high risk of recurrence and poor prognosis. CONCLUSIONS: This is the first report to suggest that a circulating snRNA can serve as an auxiliary diagnostic tool for monitoring tumor dynamics in ovarian cancer. Our results provide a rationale to further investigate whether this high-risk patient group may benefit from additional therapies that are directly applied after chemotherapy.
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Circulating U2 Small Nuclear RNA fragments as a novel diagnostic biomarker for pancreatic and colorectal adenocarcinoma
International journal of cancer, 2012Co-Authors: Alexander Baraniskin, Stefanie Nöpel-dünnebacke, Maike Ahrens, Steffen Grann Jensen, Hannah Zöllner, Abdelouahid Maghnouj, Alexandra Wos, Julia Mayerle, Johanna Munding, Dennis KostAbstract:Improved non-invasive strategies for early cancer detection are urgently needed to reduce morbidity and mortality. Non-coding RNAs, such as microRNAs and Small nucleolar RNAs, have been proposed as biomarkers for non-invasive cancer diagnosis. Analyzing serum derived from nude mice implanted with primary human pancreatic ductal adenocarcinoma (PDAC), we identified 15 diagnostic microRNA candidates. Of those miR-1246 was selected based on its high abundance in serum of tumor carrying mice. Subsequently, we noted a cross reactivity of the established miR-1246 assays with RNA fragments derived from U2 Small Nuclear RNA (RNU2-1). Importantly, we found that the assay signal discriminating tumor from controls was derived from U2 Small Nuclear RNA (snRNA) fragments (RNU2-1f) and not from miR-1246. In addition, we observed a remarkable stability of RNU2-1f in serum and provide experimental evidence that hsa-miR-1246 is likely a pseudo microRNA. In a next step, RNU2-1f was measured by qRT-PCR and normalized to cel-54 in 191 serum/plasma samples from PDAC and colorectal carcinoma (CRC) patients. In comparison to 129 controls, we were able to classify samples as cancerous with a sensitivity and specificity of 97.7% [95% CI = (87.7, 99.9)] and 90.6% [95% CI = (80.7, 96.5)], respectively [area under the ROC curve 0.972]. Of note, patients with CRC were detected with our assay as early as UICC Stage II with a sensitivity of 81%. In conclusion, this is the first report showing that fragments of U2 snRNA are highly stable in serum and plasma and may serve as novel diagnostic biomarker for PDAC and CRC for future prospective screening studies.
