CK2 phosphorylation of CMTR1 promotes RNA cap formation and influenza virus infection
Abstract
The RNA cap methyltransferase CMTR1 methylates the first transcribed nucleotide of RNA polymerase II transcripts, impacting gene expression mechanisms, including during innate immune responses. Using mass spectrometry, we identify a multiply phosphorylated region of CMTR1 (phospho-patch [P-Patch]), which is a substrate for the kinase CK2 (casein kinase II). CMTR1 phosphorylation alters intramolecular interactions, increases recruitment to RNA polymerase II, and promotes RNA cap methylation. P-Patch phosphorylation occurs during the G1 phase of the cell cycle, recruiting CMTR1 to RNA polymerase II during a period of rapid transcription and RNA cap formation. CMTR1 phosphorylation is required for the expression of specific RNAs, including ribosomal protein gene transcripts, and promotes cell proliferation. CMTR1 phosphorylation is also required for interferon-stimulated gene expression. The cap-snatching virus, influenza A, utilizes host CMTR1 phosphorylation to produce the caps required for virus production and infection. We present an RNA cap methylation control mechanism whereby CK2 controls CMTR1, enhancing co-transcriptional capping.
Citation
Lukoszek , R , Inesta-Vaquera , F , Brett , N J M , Liang , S , Hepburn , L A , Hughes , D J , Pirillo , C , Roberts , E W & Cowling , V H 2024 , ' CK2 phosphorylation of CMTR1 promotes RNA cap formation and influenza virus infection ' , Cell Reports , vol. 43 , no. 7 , 114405 . https://doi.org/10.1016/j.celrep.2024.114405
Publication
Cell Reports
Status
Peer reviewed
ISSN
2211-1247Type
Journal article
Description
Funding: This work was supported by Cancer Research UK core grant number A17196/A31287 to the CRUK Scotland Institute and CTRQQR-2021\100006 to the CRUK Scotland Centre. Research was funded by European Research Council Award 769080 TCAPS, Medical Research Council Senior Fellowship MR/K024213/1, a Lister Research Prize Fellowship, a Wellcome Trust PhD studentship 097462/Z/11/Z, Royal Society Wolfson Research Merit Award WRM\R1\180008, Wellcome Trust Investigator Award 219416/A/19/Z, and Wellcome Trust GRE Centre Award 097945/Z/11/Z.Collections
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.