DHX15 regulates CMTR1-dependent gene expression and cell proliferation

Francisco Inesta-Vaquera, Viduth K. Chaugule, Alison Galloway, Laurel Chandler, Alejandro Rojas-Fernandez, Simone Weidlich, Mark Peggie, Victoria Cowling (Lead / Corresponding author)

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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.

Original languageEnglish
Article numbere201800092
Number of pages18
JournalLife Science Alliance
Volume1
Issue number3
DOIs
Publication statusPublished - 18 Jun 2018

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