ZC3H4 restricts non-coding transcription in human cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA684332 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13239424.fastq.gz | Fastqsanger.gz | |||
| SRR13239425.fastq.gz | Fastqsanger.gz | |||
| SRR13239426.fastq.gz | Fastqsanger.gz | |||
| SRR13239427.fastq.gz | Fastqsanger.gz | |||
| SRR13239428.fastq.gz | Fastqsanger.gz |
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Project description:The human genome encodes many thousands of non-coding RNAs. A majority of these are curtailed by early transcriptional termination followed by rapid degradation. The mechanisms and factors responsible for restricting non-coding transcription in this fashion are poorly characterised, but these RNAs vastly outnumbering those with coding potential. We identify ZC3H4 as a metazoan-specific factor controlling the level and extent of hundreds of unstable transcripts. The most striking effects are for antisense RNAs and those transcribed from super-enhancers, but a subset of protein-coding RNAs are also affected. ZC3H4 occupies these genomic loci and its level of recruitment correlates with RNA extension observed in its absence. Finally, engineered targeting of ZC3H4 to an otherwise unaffected RNA supresses its production and leads to rapid degradation, endowing it with the features associated with its natural targets. We conclude that ZC3H4 is a hitherto uncharacterised factor that restricts unproductive transcription.
2021-08-06 | GSE163015 | GEO
Project description:The human genome encodes thousands of non-coding RNAs. Many of these terminate early and are then rapidly degraded, but how their transcription is restricted is poorly understood. In a screen for protein-coding gene transcriptional termination factors, we identified ZC3H4. Its depletion causes upregulation and extension of hundreds of unstable transcripts, particularly antisense RNAs and those transcribed from so-called super-enhancers. These loci are occupied by ZC3H4, suggesting that it directly functions in their transcription. Consistently, engineered tethering of ZC3H4 to reporter RNA promotes its degradation by the exosome. ZC3H4 is predominantly metazoan -interesting when considering its impact on enhancer RNAs that are less prominent in single-celled organisms. Finally, ZC3H4 loss causes a substantial reduction in cell proliferation, highlighting its overall importance. In summary, we identify ZC3H4 as playing an important role in restricting non-coding transcription in multicellular organisms.
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Project description:There are thousands of unstable non-coding (nc) RNAs in humans, but their transcriptional regulation is poorly characterized compared to protein-coding transcripts. We recently identified a restrictor complex containing ZC3H4 and WDR82, which terminates non-coding transcription. Here we show that the ncRNA termination factor, ARS2, and the nuclear exosome targeting complex (NEXT) are part of this complex. ARS2/NEXT and WDR82 contact different parts of ZC3H4, which are required for its transcription regulatory function. They facilitate ZC3H4-mediated termination by different mechanisms: ARS2 aids substrate targeting and WDR82 mediates RNA polymerase II interaction. ZC3H4 and WDR82 predominantly affect antisense, unstable, and intragenic ncRNAs. We provide an explanation for this by showing that U1 telescripting shields hundreds of protein-coding transcripts from their termination functions. We have defined an expanded ZC3H4 restrictor complex, its principles of action, and how protein-coding transcripts evade it.
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Project description:There are thousands of unstable non-coding (nc) RNAs in humans, but their transcriptional regulation is poorly characterized compared to protein-coding transcripts. We recently identified a restrictor complex containing ZC3H4 and WDR82, which terminates non-coding transcription. Here we show that the ncRNA termination factor, ARS2, and the nuclear exosome targeting complex (NEXT) are part of this complex. ARS2/NEXT and WDR82 contact different parts of ZC3H4, which are required for its transcription regulatory function. They facilitate ZC3H4-mediated termination by different mechanisms: ARS2 aids substrate targeting and WDR82 mediates RNA polymerase II interaction. ZC3H4 and WDR82 predominantly affect antisense, unstable, and intragenic ncRNAs. We provide an explanation for this by showing that U1 telescripting shields hundreds of protein-coding transcripts from their termination functions. We have defined an expanded ZC3H4 restrictor complex, its principles of action, and how protein-coding transcripts evade it.
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Project description:There are thousands of unstable non-coding (nc) RNAs in humans, but their transcriptional regulation is poorly characterized compared to protein-coding transcripts. We recently identified a restrictor complex containing ZC3H4 and WDR82, which terminates non-coding transcription. Here we show that the ncRNA termination factor, ARS2, and the nuclear exosome targeting complex (NEXT) are part of this complex. ARS2/NEXT and WDR82 contact different parts of ZC3H4, which are required for its transcription regulatory function. They facilitate ZC3H4-mediated termination by different mechanisms: ARS2 aids substrate targeting and WDR82 mediates RNA polymerase II interaction. ZC3H4 and WDR82 predominantly affect antisense, unstable, and intragenic ncRNAs. We provide an explanation for this by showing that U1 telescripting shields hundreds of protein-coding transcripts from their termination functions. We have defined an expanded ZC3H4 restrictor complex, its principles of action, and how protein-coding transcripts evade it.
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Project description:There are thousands of unstable non-coding (nc) RNAs in humans, but their transcriptional regulation is poorly characterized compared to protein-coding transcripts. We recently identified a restrictor complex containing ZC3H4 and WDR82, which terminates non-coding transcription. Here we show that the ncRNA termination factor, ARS2, and the nuclear exosome targeting complex (NEXT) are part of this complex. ARS2/NEXT and WDR82 contact different parts of ZC3H4, which are required for its transcription regulatory function. They facilitate ZC3H4-mediated termination by different mechanisms: ARS2 aids substrate targeting and WDR82 mediates RNA polymerase II interaction. ZC3H4 and WDR82 predominantly affect antisense, unstable, and intragenic ncRNAs. We provide an explanation for this by showing that U1 telescripting shields hundreds of protein-coding transcripts from their termination functions. We have defined an expanded ZC3H4 restrictor complex, its principles of action, and how protein-coding transcripts evade it.
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Project description:There are thousands of unstable non-coding (nc) RNAs in humans, but their transcriptional regulation is poorly characterized compared to protein-coding transcripts. We recently identified a restrictor complex containing ZC3H4 and WDR82, which terminates non-coding transcription. Here we show that the ncRNA termination factor, ARS2, and the nuclear exosome targeting complex (NEXT) are part of this complex. ARS2/NEXT and WDR82 contact different parts of ZC3H4, which are required for its transcription regulatory function. They facilitate ZC3H4-mediated termination by different mechanisms: ARS2 aids substrate targeting and WDR82 mediates RNA polymerase II interaction. ZC3H4 and WDR82 predominantly affect antisense, unstable, and intragenic ncRNAs. We provide an explanation for this by showing that U1 telescripting shields hundreds of protein-coding transcripts from their termination functions. We have defined an expanded ZC3H4 restrictor complex, its principles of action, and how protein-coding transcripts evade it.
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Project description:There are thousands of unstable non-coding (nc) RNAs in humans, but their transcriptional regulation is poorly characterized compared to protein-coding transcripts. We recently identified a restrictor complex containing ZC3H4 and WDR82, which terminates non-coding transcription. Here we show that the ncRNA termination factor, ARS2, and the nuclear exosome targeting complex (NEXT) are part of this complex.ARS2/NEXT and WDR82 contact different parts of ZC3H4, which are required for its transcription regulatory function. They facilitateZC3H4-mediated termination by different mechanisms: ARS2 aids substrate targeting and WDR82 mediates RNA polymerase II interaction.ZC3H4 and WDR82 predominantly affect antisense, unstable, and intragenic ncRNAs. We provide an explanation for this by showing that U1 telescripting shields hundreds of protein-coding transcripts from their termination functions.We have defined an expanded ZC3H4 restrictor complex, its principles of action, and how protein-coding transcripts evade it.
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Project description:There are thousands of unstable non-coding (nc) RNAs in humans, but their transcriptional regulation is poorly characterized compared to protein-coding transcripts. We recently identified a restrictor complex containing ZC3H4 and WDR82, which terminates non-coding transcription. Here we show that the ncRNA termination factor, ARS2, and the nuclear exosome targeting complex (NEXT) are part of this complex.ARS2/NEXT and WDR82 contact different parts of ZC3H4, which are required for its transcription regulatory function. They facilitateZC3H4-mediated termination by different mechanisms: ARS2 aids substrate targeting and WDR82 mediates RNA polymerase II interaction.ZC3H4 and WDR82 predominantly affect antisense, unstable, and intragenic ncRNAs. We provide an explanation for this by showing that U1 telescripting shields hundreds of protein-coding transcripts from their termination functions.We have defined an expanded ZC3H4 restrictor complex, its principles of action, and how protein-coding transcripts evade it.
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