Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA292106 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2147735.fastq.gz | Fastqsanger.gz | |||
| SRR2147736.fastq.gz | Fastqsanger.gz | |||
| SRR2147737.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 3 of 3 |
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Project description:Transcription and splicing are intricately linked processes, with emerging evidence highlighting the involvement of splicing factors mediating their coupling. U1 small nuclear ribonucleoprotein particle (U1 snRNP), a key splicing factor, not only serves as the initial component of the spliceosome but also plays a crucial role in preventing premature cleavage and polyadenylation, facilitating long-distance transcription elongation. Here, we show that U1 snRNP regulates alternative promoter usage through inhibition of premature polyadenylation. Inhibiting U1 snRNP with antisense oligonucleotides or introducing a premature polyadenylation leads to a significant decrease in downstream promoter activity in genes with premature polyadenylation sites in between two promoters. Conversely, restoring U1 snRNP activity or inhibiting premature polyadenylation sites using a gene-specific U1 snRNP rescues downstream promoter activity. Mechanistically, U1 snRNP inhibition correlates with reduced chromatin accessibility and serine 5 phosphorylation levels of RNA polymerase II at downstream promoters. Our findings propose a model where U1 snRNP facilitates productive transcription from upstream promoters, triggering downstream promoter activation by destabilizing nucleosomes and promoting promoter escape.
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Project description:Transcription and splicing are intricately linked processes, with emerging evidence highlighting the involvement of splicing factors mediating their coupling. U1 small nuclear ribonucleoprotein particle (U1 snRNP), a key splicing factor, not only serves as the initial component of the spliceosome but also plays a crucial role in preventing premature cleavage and polyadenylation, facilitating long-distance transcription elongation. Here, we show that U1 snRNP regulates alternative promoter usage through inhibition of premature polyadenylation. Inhibiting U1 snRNP with antisense oligonucleotides or introducing a premature polyadenylation leads to a significant decrease in downstream promoter activity in genes with premature polyadenylation sites in between two promoters. Conversely, restoring U1 snRNP activity or inhibiting premature polyadenylation sites using a gene-specific U1 snRNP rescues downstream promoter activity. Mechanistically, U1 snRNP inhibition correlates with reduced chromatin accessibility and serine 5 phosphorylation levels of RNA polymerase II at downstream promoters. Our findings propose a model where U1 snRNP facilitates productive transcription from upstream promoters, triggering downstream promoter activation by destabilizing nucleosomes and promoting promoter escape.
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Project description:Synaptic activity induces well-known changes in enhancer-promoter driven gene expression but also induces changes in splicing and polyadenylation that are understudied. Here, we investigate the mechanism of expression for alternative polyadenylation isoform Homer1a, an immediate early gene essential to synaptic plasticity. We report that neuronal activation, in neuronal cultures and in adult mouse brain, depletes the splice factor U1 snRNP from Homer1 pre-mRNA and that this causes shifted utilization of a cryptic polyadenylation signal within intron 5 resulting in Homer1a expression. Because U1 snRNP is a ubiquitous splice factor, we tested the generality of activity-driven U1 snRNP depletion as a mechanism for gene expression using RNA immunoprecipitation sequencing. Analysis reveals that neuronal activity changes U1 snRNP binding to ~2000 transcripts and for a subset of transcripts, a reduction in U1 snRNP binding was accompanied by utilization of a cryptic intronic polyadenylation site. This subset is enriched for transcripts encoding synaptic proteins involved in excitability control. Genes demonstrating activity-dependent reduced U1 snRNP binding often encode a binding motif for Sam68, a neuronal alternative polyadenylation factor. Findings reveal that activity-driven changes in intron utilization for transcript termination serves an important role in synaptic plasticity.
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Project description:Transcription and splicing are inherently intertwined. Accumulating evidence support a role of splicing factors in mediating this coupling. U1 small nuclear ribonucleoprotein particle (U1 snRNP), a key splicing factor, acts as the initial building block of the spliceosome, interacting with nascent pre-mRNA at 5' splice sites. In addition to its role in splicing, U1 snRNP is crucial for preventing premature cleavage and polyadenylation, enabling long-distance transcription elongation. Here, we show that U1 snRNP can regulate the usage of alternative promoters through its role in inhibiting premature polyadenylation. Using antisense oligonucleotides to inhibit U1 snRNP, we first observed a markedly decrease in downstream promoter activity at the newly synthesized RNA level. Interestingly, U1 snRNP inhibition selectively impacts downstream promoters of genes featuring premature polyadenylation sites located between two promoters. Overexpressing a wild-type U1 snRNP or a gene-specific U1 snRNP designed to inhibit premature polyadenylation sites restores downstream promoter activity. Conversely, introducing a premature polyadenylation site between two promoters reduces downstream promoter activity. Exploring the underlying molecular mechanisms, we identified a substantial decrease in serine 5 phosphorylation levels in newly recruited RNA polymerase II at downstream promoters following U1 snRNP inhibition, and reduced chromatin accessibility in the vicinity of downstream promoters. Overall, our model is consistent with productive transcription from upstream promoters triggering downstream promoter activation in the presence of U1 snRNP by destabilizing nucleosomes and promoting promoter escape at downstream promoters.
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Project description:Transcription and splicing are inherently intertwined. Accumulating evidence support a role of splicing factors in mediating this coupling. U1 small nuclear ribonucleoprotein particle (U1 snRNP), a key splicing factor, acts as the initial building block of the spliceosome, interacting with nascent pre-mRNA at 5' splice sites. In addition to its role in splicing, U1 snRNP is crucial for preventing premature cleavage and polyadenylation, enabling long-distance transcription elongation. Here, we show that U1 snRNP can regulate the usage of alternative promoters through its role in inhibiting premature polyadenylation. Using antisense oligonucleotides to inhibit U1 snRNP, we first observed a markedly decrease in downstream promoter activity at the newly synthesized RNA level. Interestingly, U1 snRNP inhibition selectively impacts downstream promoters of genes featuring premature polyadenylation sites located between two promoters. Overexpressing a wild-type U1 snRNP or a gene-specific U1 snRNP designed to inhibit premature polyadenylation sites restores downstream promoter activity. Conversely, introducing a premature polyadenylation site between two promoters reduces downstream promoter activity. Exploring the underlying molecular mechanisms, we identified a substantial decrease in serine 5 phosphorylation levels in newly recruited RNA polymerase II at downstream promoters following U1 snRNP inhibition, and reduced chromatin accessibility in the vicinity of downstream promoters. Overall, our model is consistent with productive transcription from upstream promoters triggering downstream promoter activation in the presence of U1 snRNP by destabilizing nucleosomes and promoting promoter escape at downstream promoters.
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Project description:Transcription and splicing are inherently intertwined. Accumulating evidence support a role of splicing factors in mediating this coupling. U1 small nuclear ribonucleoprotein particle (U1 snRNP), a key splicing factor, acts as the initial building block of the spliceosome, interacting with nascent pre-mRNA at 5' splice sites. In addition to its role in splicing, U1 snRNP is crucial for preventing premature cleavage and polyadenylation, enabling long-distance transcription elongation. Here, we show that U1snRNP can regulate the usage of alternative promoters through its role in inhibiting premature polyadenylation. Using antisense oligonucleotides to inhibit U1 snRNP, we first observed a markedly decrease in downstream promoter activity at the newly synthesized RNA level. Interestingly, U1 snRNP inhibition selectively impacts downstream promoters of genes featuring premature polyadenylation sites located between two promoters. Overexpressing a wild-type U1 snRNP or a gene-specific U1 snRNP designed to inhibit premature polyadenylation sites restores downstream promoter activity. Conversely, introducing a premature polyadenylation site between two promoters reduces downstream promoter activity. Exploring the underlying molecular mechanisms, we identified a substantial decrease in serine 5 phosphorylation levels in newly recruited RNA polymerase II at downstream promoters following U1 snRNP inhibition, and reduced chromatin accessibility in the vicinity of downstream promoters. Overall, our model is consistent with productive transcription from upstream promoters triggering downstream promoter activation in the presence of U1 snRNP by destabilizing nucleosomes and promoting promoter escape at downstream promoters.
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Project description:U1 snRNP regulates alternative promoter activity by inhibiting premature polyadenylation
| PRJNA1060322 | ENA
Project description:U1 snRNP regulates alternative promoter activity by inhibiting premature polyadenylation
| PRJNA1200036 | ENA
Project description:The DNA damage response (DDR) involves coordinated control of gene expression and DNA repair. Using deep sequencing we found widespread changes of alternative cleavage and polyadenylation (APA) site usage upon UV-treatment in mammalian cells. APA regulation in the 3’ untranslated region (3’UTR) is substantial, leading to both shortening and lengthening of 3’UTRs. Interestingly, a strong activation of intronic APA sites is detected, resulting in widespread expression of truncated transcripts. Intronic APA events are biased to the 5’ end of genes and affect gene groups with important functions in DDR. Moreover, intronic APA site activation during DDR correlates with a decrease in U1 snRNA levels, and this is reversed by U1 snRNA overexpression. Importantly, U1 snRNA overexpression decreases UV-induced apoptosis. Together, these studies describe a significant gene regulatory scheme in DDR where U1 snRNP impacts gene expression via APA.
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Project description:In eukaryotes, U1 small nuclear ribonucleoprotein (snRNP) forms spliceosomes in equal stoichiometry with U2, U4, U5 and U6 snRNPs; however, its abundance in human far exceeds that of the other snRNPs. Here we used antisense morpholino oligonucleotide to U1 snRNA to achieve functional U1 snRNP knockdown in HeLa cells, and identified accumulated unspliced pre-mRNAs by genomic tiling microarrays. In addition to inhibiting splicing, U1 snRNP knockdown caused premature cleavage and polyadenylation in numerous pre-mRNAs at cryptic polyadenylation signals, frequently in introns near (<5 kilobases) the start of the transcript. This did not occur when splicing was inhibited with U2 snRNA antisense morpholino oligonucleotide or the U2-snRNP-inactivating drug spliceostatin A unless U1 antisense morpholino oligonucleotide was also included. We further show that U1 snRNA–pre-mRNA base pairing was required to suppress premature cleavage and polyadenylation from nearby cryptic polyadenylation signals located in introns. These findings reveal a critical splicing-independent function for U1 snRNP in protecting the transcriptome, which we propose explains its overabundance.
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