PAPγ associates with PAXT nuclear exosome to control the abundance of PROMPT ncRNAs
Abstract Pervasive transcription of the human genome generates an abundance of RNAs that must be processed and degraded. The nuclear RNA exosome is the main RNA degradation machinery in the nucleus. However, nuclear exosome must be recruited to its substrates by targeting complexes, such as NEXT or...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42620-9 |
| _version_ | 1797558110051631104 |
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| author | Xavier Contreras David Depierre Charbel Akkawi Marina Srbic Marion Helsmoortel Maguelone Nogaret Matthieu LeHars Kader Salifou Alexandre Heurteau Olivier Cuvier Rosemary Kiernan |
| author_facet | Xavier Contreras David Depierre Charbel Akkawi Marina Srbic Marion Helsmoortel Maguelone Nogaret Matthieu LeHars Kader Salifou Alexandre Heurteau Olivier Cuvier Rosemary Kiernan |
| author_sort | Xavier Contreras |
| collection | DOAJ |
| description | Abstract Pervasive transcription of the human genome generates an abundance of RNAs that must be processed and degraded. The nuclear RNA exosome is the main RNA degradation machinery in the nucleus. However, nuclear exosome must be recruited to its substrates by targeting complexes, such as NEXT or PAXT. By proteomic analysis, we identify additional subunits of PAXT, including many orthologs of MTREC found in S. pombe. In particular, we show that polyA polymerase gamma (PAPγ) associates with PAXT. Genome-wide mapping of the binding sites of ZFC3H1, RBM27 and PAPγ shows that PAXT is recruited to the TSS of hundreds of genes. Loss of ZFC3H1 abolishes recruitment of PAXT subunits including PAPγ to TSSs and concomitantly increases the abundance of PROMPTs at the same sites. Moreover, PAPγ, as well as MTR4 and ZFC3H1, is implicated in the polyadenylation of PROMPTs. Our results thus provide key insights into the direct targeting of PROMPT ncRNAs by PAXT at their genomic sites. |
| first_indexed | 2024-03-10T17:25:48Z |
| format | Article |
| id | doaj.art-dead10e00ef946ad9aa32b08b538a230 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:25:48Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-dead10e00ef946ad9aa32b08b538a2302023-11-20T10:11:34ZengNature PortfolioNature Communications2041-17232023-10-0114111410.1038/s41467-023-42620-9PAPγ associates with PAXT nuclear exosome to control the abundance of PROMPT ncRNAsXavier Contreras0David Depierre1Charbel Akkawi2Marina Srbic3Marion Helsmoortel4Maguelone Nogaret5Matthieu LeHars6Kader Salifou7Alexandre Heurteau8Olivier Cuvier9Rosemary Kiernan10CNRS-UMR 9002, Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation LabCenter of Integrative Biology (CBI-CNRS), Molecular, Cellular and Developmental Biology (MCD Unit), University of ToulouseCNRS-UMR 9002, Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation LabCNRS-UMR 9002, Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation LabCNRS-UMR 9002, Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation LabCNRS-UMR 9002, Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation LabCNRS-UMR 9002, Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation LabCNRS-UMR 9002, Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation LabCenter of Integrative Biology (CBI-CNRS), Molecular, Cellular and Developmental Biology (MCD Unit), University of ToulouseCenter of Integrative Biology (CBI-CNRS), Molecular, Cellular and Developmental Biology (MCD Unit), University of ToulouseCNRS-UMR 9002, Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation LabAbstract Pervasive transcription of the human genome generates an abundance of RNAs that must be processed and degraded. The nuclear RNA exosome is the main RNA degradation machinery in the nucleus. However, nuclear exosome must be recruited to its substrates by targeting complexes, such as NEXT or PAXT. By proteomic analysis, we identify additional subunits of PAXT, including many orthologs of MTREC found in S. pombe. In particular, we show that polyA polymerase gamma (PAPγ) associates with PAXT. Genome-wide mapping of the binding sites of ZFC3H1, RBM27 and PAPγ shows that PAXT is recruited to the TSS of hundreds of genes. Loss of ZFC3H1 abolishes recruitment of PAXT subunits including PAPγ to TSSs and concomitantly increases the abundance of PROMPTs at the same sites. Moreover, PAPγ, as well as MTR4 and ZFC3H1, is implicated in the polyadenylation of PROMPTs. Our results thus provide key insights into the direct targeting of PROMPT ncRNAs by PAXT at their genomic sites.https://doi.org/10.1038/s41467-023-42620-9 |
| spellingShingle | Xavier Contreras David Depierre Charbel Akkawi Marina Srbic Marion Helsmoortel Maguelone Nogaret Matthieu LeHars Kader Salifou Alexandre Heurteau Olivier Cuvier Rosemary Kiernan PAPγ associates with PAXT nuclear exosome to control the abundance of PROMPT ncRNAs Nature Communications |
| title | PAPγ associates with PAXT nuclear exosome to control the abundance of PROMPT ncRNAs |
| title_full | PAPγ associates with PAXT nuclear exosome to control the abundance of PROMPT ncRNAs |
| title_fullStr | PAPγ associates with PAXT nuclear exosome to control the abundance of PROMPT ncRNAs |
| title_full_unstemmed | PAPγ associates with PAXT nuclear exosome to control the abundance of PROMPT ncRNAs |
| title_short | PAPγ associates with PAXT nuclear exosome to control the abundance of PROMPT ncRNAs |
| title_sort | papγ associates with paxt nuclear exosome to control the abundance of prompt ncrnas |
| url | https://doi.org/10.1038/s41467-023-42620-9 |
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