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Science Advances
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Article . 2023
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7SK methylation by METTL3 promotes transcriptional activity

Authors: Marcelo Perez-Pepe; Anthony W. Desotell; Hengyi Li; Wenxue Li; Bing Han; Qishan Lin; Daryl E. Klein; +3 Authors

7SK methylation by METTL3 promotes transcriptional activity

Abstract

A fundamental feature of cell signaling is the conversion of extracellular signals into adaptive transcriptional responses. The role of RNA modifications in this process is poorly understood. The small nuclear RNA 7SK prevents transcriptional elongation by sequestering the cyclin dependent kinase 9/cyclin T1 (CDK9/CCNT1) positive transcription elongation factor (P-TEFb) complex. We found that epidermal growth factor signaling induces phosphorylation of the enzyme methyltransferase 3 (METTL3), leading to METTL3-mediated methylation of 7SK. 7SK methylation enhanced its binding to heterogeneous nuclear ribonucleoproteins, causing the release of the HEXIM1 P-TEFb complex subunit1 (HEXIM1)/P-TEFb complex and inducing transcriptional elongation. Our findings establish the mechanism underlying 7SK activation and uncover a previously unknown function for the m 6 A modification in converting growth factor signaling events into a regulatory transcriptional response via an RNA methylation–dependent switch.

Country
United States
Keywords

570, Transcription, Genetic, 1.1 Normal biological development and functioning, 610, RNA-Binding Proteins, Methyltransferases, Biological Sciences, Methylation, Small Nuclear, Genetic, Underpinning research, RNA, Small Nuclear, Genetics, RNA, Humans, Positive Transcriptional Elongation Factor B, Biochemistry and Cell Biology, Generic health relevance, Biomedicine and Life Sciences, Transcription, Transcription Factors

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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
20
Top 10%
Average
Top 10%
Green
gold