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- W4306755812 abstract "Abstract A fundamental facet 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 transcription elongation by sequestering the complex CDK9/CCNT1 (P-TEFb). We discovered that METTL3 methylates 7SK. The m 6 A methylation of 7SK in turn promotes its binding to heterogeneous nuclear ribonucleoproteins (HNRNPs), with consequent release of the HEXIM1/P-TEFb complex – leading to the induction of growth factor-stimulated transcriptional responses. The methylation of 7SK relies on the activation of METTL3 via phosphorylation downstream of growth factors-signaling pathways such as the epidermal growth factor (EGF). Our findings establish a novel function for the m 6 A modification in converting growth-factor signaling events to a transcriptional elongation regulatory response via an RNA-methylation-dependent switch. One-Sentence Summary m 6 A methylation of the non-coding RNA 7SK promotes transcriptional activity upon growth factor stimulation." @default.
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- W4306755812 date "2022-10-18" @default.
- W4306755812 modified "2023-09-25" @default.
- W4306755812 title "7SK methylation Promotes Transcriptional Activity" @default.
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- W4306755812 doi "https://doi.org/10.1101/2022.10.17.512631" @default.
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