PT  - JOURNAL ARTICLE
AU  - Francisco Inesta-Vaquera
AU  - Viduth K Chaugule
AU  - Alison Galloway
AU  - Laurel Chandler
AU  - Alejandro Rojas-Fernandez
AU  - Simone Weidlich
AU  - Mark Peggie
AU  - Victoria H Cowling
TI  - DHX15 regulates CMTR1-dependent gene expression and cell proliferation
AID  - 10.26508/lsa.201800092
DP  - 2018 Jun 01
TA  - Life Science Alliance
PG  - e201800092
VI  - 1
IP  - 3
4099  - https://www.life-science-alliance.org/content/1/3/e201800092.short
4100  - https://www.life-science-alliance.org/content/1/3/e201800092.full
SO  - Life Sci. Alliance2018 Jun 01; 1
AB  - 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 methyltransferase 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.