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DHX15 regulates CMTR1-dependent gene expression and cell proliferation.


ABSTRACT: CMTR1 contributes to mRNA cap formation by methylating the first transcribed nucleotide ribose at the O-2 position. mRNA cap O-2 methylation has roles in mRNA stabilisation and translation, and self-RNA tolerance in innate immunity. We report that CMTR1 is recruited to serine-5-phosphorylated RNA Pol II C-terminal domain, early in transcription. We isolated CMTR1 in a complex with DHX15, an RNA helicase functioning in splicing and ribosome biogenesis, and characterised it as a regulator of CMTR1. When DHX15 is bound, CMTR1 activity is repressed and the methyl-transferase does not bind to RNA pol II. Conversely, CMTR1 activates DHX15 helicase activity, which is likely to impact several nuclear functions. In HCC1806 breast carcinoma cell line, the DHX15-CMTR1 interaction controls ribosome loading of a subset of mRNAs and regulates cell proliferation. The impact of the CMTR1-DHX15 interaction is complex and will depend on the relative expression of these enzymes and their interactors, and the cellular dependency on different RNA processing pathways.

SUBMITTER: Inesta-Vaquera F 

PROVIDER: S-EPMC6071836 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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DHX15 regulates CMTR1-dependent gene expression and cell proliferation.

Inesta-Vaquera Francisco F   Chaugule Viduth K VK   Galloway Alison A   Chandler Laurel L   Rojas-Fernandez Alejandro A   Weidlich Simone S   Peggie Mark M   Cowling Victoria H VH  

Life science alliance 20180601 3


CMTR1 contributes to mRNA cap formation by methylating the first transcribed nucleotide ribose at the O-2 position. mRNA cap O-2 methylation has roles in mRNA stabilisation and translation, and self-RNA tolerance in innate immunity. We report that CMTR1 is recruited to serine-5-phosphorylated RNA Pol II C-terminal domain, early in transcription. We isolated CMTR1 in a complex with DHX15, an RNA helicase functioning in splicing and ribosome biogenesis, and characterised it as a regulator of CMTR1  ...[more]

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