Genome-wide analysis of the SNAPc complex [ChIP-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE37403 | GEO | 2012/09/28
SECONDARY ACCESSION(S): PRJNA159777
REPOSITORIES: GEO
Similar Datasets
Project description:The small nuclear RNA (snRNA)-activating protein complex (SNAPc) is a basal transcription factor that mediates the transcriptional activation of snRNAs. Here, we describe the genome-wide occupancy of the SNAPC1 and SNAPC4 subunits of SNAPc. While the SNAPC4 occupancy was in accord with the role for SNAPc in snRNA transcription, SNAPC1 displayed a broader genomic profile mirroring that of RNA polymerase II at highly active protein-coding genes. Our functional analysis revealed a role for SNAPc1 in regulation of both basal and activator-induced transcription of protein-coding genes. These studies expand the role for SNAPC1 beyond its regulation of snRNA transcription. Comparison of the genome wide profiles of different SNAPc subunits and RNAPII in human cells
2012-09-28 | E-GEOD-37403 | biostudies-arrayexpress
Project description:The small nuclear RNA (snRNA)-activating protein complex (SNAPc) is a basal transcription factor that mediates the transcriptional activation of snRNAs. Here, we describe the genome-wide occupancy of the SNAPC1_and SNAPC4 subunits of SNAPc. While the SNAPC4 occupancy was in accord with the role for SNAPc in snRNA transcription, SNAPC1_displayed a broader genomic profile mirroring that of RNA polymerase II at highly active protein-coding genes. Our functional analysis revealed a role for SNAPC1_in regulation of both basal and activator-induced transcription of protein-coding genes. These studies expand the role for SNAPC1_beyond its regulation of snRNA transcription. EGF stimulation of Hela cells, transfected with a control sh (scr) or a SNAPC1_sh
2012-10-12 | E-GEOD-41528 | biostudies-arrayexpress
Project description:The small nuclear RNA (snRNA)-activating protein complex (SNAPc) is a basal transcription factor that mediates the transcriptional activation of snRNAs. Here, we describe the genome-wide occupancy of the SNAPC1_and SNAPC4 subunits of SNAPc. While the SNAPC4 occupancy was in accord with the role for SNAPc in snRNA transcription, SNAPC1_displayed a broader genomic profile mirroring that of RNA polymerase II at highly active protein-coding genes. Our functional analysis revealed a role for SNAPC1_in regulation of both basal and activator-induced transcription of protein-coding genes. These studies expand the role for SNAPC1_beyond its regulation of snRNA transcription.
2012-10-12 | GSE41528 | GEO
Project description:RNA Polymerase II (Pol II) carries out transcription of both protein-coding and non-coding genes. Whereas Pol II initiation at protein-coding genes has been studied in detail, Pol II initiation at non-coding genes such as small nuclear RNA (snRNA) genes is not understood at the structural level. Here we study Pol II initiation at snRNA gene promoters and show that the snRNA-activating protein complex (SNAPc) enables DNA opening and transcription initiation independent of TFIIE and TFIIH in vitro. We then resolve cryo-EM structures of the SNAPc-containing Pol II preinitiation complex (PIC) assembled on U1 and U5 snRNA promoters. The core of SNAPc binds two turns of DNA and recognizes the snRNA promoter-specific proximal sequence element (PSE) located upstream of the TATA box-binding protein TBP. Two extensions of SNAPc called wing-1 and wing-2 bind TFIIA and TFIIB, respectively, explaining how SNAPc directs Pol II to snRNA promoters. Comparison of structures of closed and open promoter complexes elucidates TFIIH-independent DNA opening. These results provide the structural basis of Pol II initiation at non-coding RNA gene promoters.
2023-03-11 | PXD033638 | Pride
Project description:Competing exonucleases that promote 3’ end maturation or degradation direct quality control of small non-coding RNAs, but how these enzymes distinguish normal from aberrant RNAs is poorly understood. The Pontocerebellar Hypoplasia 7 (PCH7)-associated 3’ exonuclease TOE1 promotes maturation of canonical small nuclear RNAs (snRNAs). Here, we demonstrate that TOE1 achieves specificity towards canonical snRNAs by recognizing Sm complex assembly and cap trimethylation, two features that distinguish snRNAs undergoing correct biogenesis from other small non-coding RNAs. Indeed, disruption of Sm complex assembly via snRNA mutations or protein depletions obstructs snRNA processing by TOE1, and in vitro snRNA processing by TOE1 is stimulated by a trimethylated cap. An unstable snRNA variant that normally fails to undergo maturation becomes fully processed by TOE1 when its degenerate Sm binding motif is converted into a canonical one. Our findings uncover the molecular basis for how TOE1 distinguishes snRNAs from other small non-coding RNAs and explain how TOE1 promotes maturation specifically of canonical snRNAs undergoing proper processing.
2023-09-06 | GSE240773 | GEO
Project description:Competing exonucleases that promote 3’ end maturation or degradation direct quality control of small non-coding RNAs, but how these enzymes distinguish normal from aberrant RNAs is poorly understood. The Pontocerebellar Hypoplasia 7 (PCH7)-associated 3’ exonuclease TOE1 promotes maturation of canonical small nuclear RNAs (snRNAs). Here, we demonstrate that TOE1 achieves specificity towards canonical snRNAs by recognizing Sm complex assembly and cap trimethylation, two features that distinguish snRNAs undergoing correct biogenesis from other small non-coding RNAs. Indeed, disruption of Sm complex assembly via snRNA mutations or protein depletions obstructs snRNA processing by TOE1, and in vitro snRNA processing by TOE1 is stimulated by a trimethylated cap. An unstable snRNA variant that normally fails to undergo maturation becomes fully processed by TOE1 when its degenerate Sm binding motif is converted into a canonical one. Our findings uncover the molecular basis for how TOE1 distinguishes snRNAs from other small non-coding RNAs and explain how TOE1 promotes maturation specifically of canonical snRNAs undergoing proper processing.
2023-09-06 | GSE240772 | GEO
Project description:SNAPc-dependent promoters are unique among cellular promoters in being very similar to each other, even though some of them recruit RNA polymerase II and other RNA polymerase III. We have examined all SNAPc-bound promoters present in the human genome. We find that there is a surprisingly small number of them, some 70 promoters. Among these, the large majority is bound by either RNA polymerase II or RNA polymerase III, as expected, but one gene hitherto considered an RNA polymerase III gene is also occupied by significant levels of RNA polymerase II, which synthesizes an RNA distinct from that synthesized by RNA polymerase III. Both RNA polymerase II and RNA polymerase III SNAPc- dependent promoters use a largely overlapping set of a few transcription activators, including GABP, a novel factor implicated in snRNA gene transcription. SNAPc-dependent promoters in the human genome
2012-11-22 | E-GEOD-38303 | biostudies-arrayexpress
Project description:Prompt and accurate responses to DNA damage are crucial for maintaining normal cellular homeostasis and avoiding cell death. These responses involve the activation of DNA repair pathways and changes in gene expression. RNA polymerase II (RNAPII) is responsible for transcribing protein-coding genes and small nuclear RNAs (snRNAs). Concurrent with transcription, pre-mRNA undergoes splicing by the spliceosome, a complex consisting of five ribonucleoproteins (snRNPs), snRNAs, and additional factors, which ensures proper pre-mRNA splicing and generation of mature mRNA, thereby promoting proteome diversity. In this study, we provide new insights into the role of HSF2 in pre-mRNA splicing and maintenance of genomic stability. We observed a significant reduction in RNAPIICTD pS7 following loss of HSF2 and this is accompanied by the inhibition of RNAPII recruitment to snRNA gene promoters and a significant reduction in snRNA transcription. Moreover, the observed reduction in snRNAs expression in cells lacking HSF2 is associated with impaired pre-mRNA splicing and several other consequences. These include a spontaneous increase in DNA damage, enhanced formation of R-loops, and elevated cellular sensitivity to ionizing radiation (IR). These findings suggest that loss of HSF2 leads to multiple disruptions in cellular processes, ultimately resulting in compromised genome stability and increased susceptibility to DNA damage. Furthermore, HSF2-deficient mice exhibit an accelerated IR-induced T cell acute lymphoblastic leukemia (T-ALL), as evidenced by the reduced snRNA levels and expression of IR-induced DNA repair genes. Our findings reveal a previously unrecognized role for HSF2 in the process of snRNA transcription and its loss highlights its pathological consequences. These features are also mirrored by the loss of the HSF2 target gene, HSP110, suggesting that HSP110 contributes, at least in part, to the phenotypes observed following HSF2 loss.
2023-08-22 | GSE241102 | GEO
Project description:In this study we investigated snRNA-mediated modulation of pre-mRNA splicing across the human transcriptome. We first quantified the relative abundance of snRNAs across a comprehensive range of healthy adult and fetal tissues, revealing a surprising variation in the relative snRNA levels both inter- and intra-tissue. To study the role of snRNAs in cancer-relevant splicing, we used breast cancer as a model, since it exhibits a high rate of aberrant splicing48, but a low frequency of mutations in the splicing machinery52. We observed fluctuations in snRNA adundance across the majority of patients, across all breast cancer subtypes. To investigate the impact of snRNA levels using a controlled system, we knocked down snRNAs in vitro, to analyze splicing both transcriptome-wide and at the level of individual exons and introns. Depletion of each specific snRNA resulted in differential splicing across more than a thousand exon junctions within mRNA transcripts. Knock-down of U1 and U2 levels was primarily associated with changes in exon inclusion rates, whereas U4 and U6 depletion predominantly caused incomplete intron removal and a resulting retention of introns in the mature mRNA. Rather than being driven by a single factor, the observed splicing changes were associated with multiple other splicing-relevant features and mechanisms, including mRNA transcription, intron size, and nucleotide composition. The snRNA-mediated changes to the splicing program were enriched within genes encoding components of core cellular pathways and processes, including multiple aspects of RNA and protein metabolism, and thereby have the potential to impact cell growth and identity. The exons and introns that were sensitive to snRNA levels displayed a high variability in splicing in vivo across primary breast cancer samples, indicating that snRNA dysregulation may contribute to aberrant splicing in cancer. We suggest that the cellular composition of snRNAs constitutes a previously unrecognized layer of splicing regulation within the cell, and that variations or disruptions in the relative abundance of the snRNAs can affect the transcriptome of both healthy and malignant cells.
2018-12-31 | GSE107163 | GEO
Project description:U1 snRNA is the small nuclear RNA that services as the backbone of U1 snRNP. Removing intron from pre-mRNA to produce mature mRNA is the core function of the U1 snRNA. As one of the most abundant small noncoding RNA in human cells – estimated to be in the region of 1x10^6 copies per human cell (Hela) – U1 snRNA level is much more abundant than the other snRNAs. However, the potential role of the different amounts of the snRNAs is still unknown. To study the function of U1 snRNA in human neurons, we used lentivirus vector to overexpression U1 snRNA. We analyzed the gene expression change and identified target genes of U1 snRNA overexpression. We uncovered a novel role of U1 snRNA in regulating gene expression in human neurons.
2020-01-01 | GSE124951 | GEO