ZC3H4 restricts non-coding transcription in human cells
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 upreg...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-04-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/67305 |
| _version_ | 1811253616790470656 |
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| author | Chris Estell Lee Davidson Pieter C Steketee Adam Monier Steven West |
| author_facet | Chris Estell Lee Davidson Pieter C Steketee Adam Monier Steven West |
| author_sort | Chris Estell |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T16:54:11Z |
| format | Article |
| id | doaj.art-db3925eccb7d4d0082a7c6bf78d0e797 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:54:11Z |
| publishDate | 2021-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-db3925eccb7d4d0082a7c6bf78d0e7972022-12-22T03:24:18ZengeLife Sciences Publications LtdeLife2050-084X2021-04-011010.7554/eLife.67305ZC3H4 restricts non-coding transcription in human cellsChris Estell0Lee Davidson1Pieter C Steketee2Adam Monier3Steven West4https://orcid.org/0000-0002-7622-9050The Living Systems Institute, University of Exeter, Exeter, United KingdomThe Living Systems Institute, University of Exeter, Exeter, United KingdomThe Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United KingdomThe Living Systems Institute, University of Exeter, Exeter, United KingdomThe Living Systems Institute, University of Exeter, Exeter, United KingdomThe 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.https://elifesciences.org/articles/67305transcription terminationnon-coding transcriptionintegratorexosomeenhancerRNA polymerase II |
| spellingShingle | Chris Estell Lee Davidson Pieter C Steketee Adam Monier Steven West ZC3H4 restricts non-coding transcription in human cells eLife transcription termination non-coding transcription integrator exosome enhancer RNA polymerase II |
| title | ZC3H4 restricts non-coding transcription in human cells |
| title_full | ZC3H4 restricts non-coding transcription in human cells |
| title_fullStr | ZC3H4 restricts non-coding transcription in human cells |
| title_full_unstemmed | ZC3H4 restricts non-coding transcription in human cells |
| title_short | ZC3H4 restricts non-coding transcription in human cells |
| title_sort | zc3h4 restricts non coding transcription in human cells |
| topic | transcription termination non-coding transcription integrator exosome enhancer RNA polymerase II |
| url | https://elifesciences.org/articles/67305 |
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