Dynamic control of chromatin-associated m6A methylation regulates nascent RNA synthesis
N6-methyladenosine (m6A) methylation is co-transcriptionally deposited on mRNA, but a possible role of m6A on transcription remains poorly understood. Here, we demonstrate that the METTL3/METTL14/WTAP m6A methyltransferase complex (MTC) is localized to many promoters and enhancers and deposits the m...
| Autori principali: | , , , , , , , , , , , , , |
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| Natura: | Journal article |
| Lingua: | English |
| Pubblicazione: |
Cell Press
2022
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| _version_ | 1826309422534623232 |
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| author | Xu, W He, C Kaye, EG Li, J Mu, M Nelson, GM Dong, L Wang, J Wu, F Shi, YG Adelman, K Lan, F Shi, Y Shen, H |
| author_facet | Xu, W He, C Kaye, EG Li, J Mu, M Nelson, GM Dong, L Wang, J Wu, F Shi, YG Adelman, K Lan, F Shi, Y Shen, H |
| author_sort | Xu, W |
| collection | OXFORD |
| description | N6-methyladenosine (m6A) methylation is co-transcriptionally deposited on mRNA, but a possible role of m6A on transcription remains poorly understood. Here, we demonstrate that the METTL3/METTL14/WTAP m6A methyltransferase complex (MTC) is localized to many promoters and enhancers and deposits the m6A modification on nascent transcripts, including pre-mRNAs, promoter upstream transcripts (PROMPTs), and enhancer RNAs. PRO-seq analyses demonstrate that nascent RNAs originating from both promoters and enhancers are significantly decreased in the METTL3-depleted cells. Furthermore, genes targeted by the Integrator complex for premature termination are depleted of METTL3, suggesting a potential antagonistic relationship between METTL3 and Integrator. Consistently, we found the Integrator complex component INTS11 elevated at promoters and enhancers upon loss of MTC or nuclear m6A binders. Taken together, our findings suggest that MTC-mediated m6A modification protects nascent RNAs from Integrator-mediated termination and promotes productive transcription, thus unraveling an unexpected layer of gene regulation imposed by RNA m6A modification. |
| first_indexed | 2024-03-07T07:35:27Z |
| format | Journal article |
| id | oxford-uuid:c813f2bc-531c-46c8-96f9-9d9fbc19442b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:35:27Z |
| publishDate | 2022 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:c813f2bc-531c-46c8-96f9-9d9fbc19442b2023-03-02T10:42:11ZDynamic control of chromatin-associated m6A methylation regulates nascent RNA synthesisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c813f2bc-531c-46c8-96f9-9d9fbc19442bEnglishSymplectic ElementsCell Press2022Xu, WHe, CKaye, EGLi, JMu, MNelson, GMDong, LWang, JWu, FShi, YGAdelman, KLan, FShi, YShen, HN6-methyladenosine (m6A) methylation is co-transcriptionally deposited on mRNA, but a possible role of m6A on transcription remains poorly understood. Here, we demonstrate that the METTL3/METTL14/WTAP m6A methyltransferase complex (MTC) is localized to many promoters and enhancers and deposits the m6A modification on nascent transcripts, including pre-mRNAs, promoter upstream transcripts (PROMPTs), and enhancer RNAs. PRO-seq analyses demonstrate that nascent RNAs originating from both promoters and enhancers are significantly decreased in the METTL3-depleted cells. Furthermore, genes targeted by the Integrator complex for premature termination are depleted of METTL3, suggesting a potential antagonistic relationship between METTL3 and Integrator. Consistently, we found the Integrator complex component INTS11 elevated at promoters and enhancers upon loss of MTC or nuclear m6A binders. Taken together, our findings suggest that MTC-mediated m6A modification protects nascent RNAs from Integrator-mediated termination and promotes productive transcription, thus unraveling an unexpected layer of gene regulation imposed by RNA m6A modification. |
| spellingShingle | Xu, W He, C Kaye, EG Li, J Mu, M Nelson, GM Dong, L Wang, J Wu, F Shi, YG Adelman, K Lan, F Shi, Y Shen, H Dynamic control of chromatin-associated m6A methylation regulates nascent RNA synthesis |
| title | Dynamic control of chromatin-associated m6A methylation regulates nascent RNA synthesis |
| title_full | Dynamic control of chromatin-associated m6A methylation regulates nascent RNA synthesis |
| title_fullStr | Dynamic control of chromatin-associated m6A methylation regulates nascent RNA synthesis |
| title_full_unstemmed | Dynamic control of chromatin-associated m6A methylation regulates nascent RNA synthesis |
| title_short | Dynamic control of chromatin-associated m6A methylation regulates nascent RNA synthesis |
| title_sort | dynamic control of chromatin associated m6a methylation regulates nascent rna synthesis |
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