Projects per year
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 language | English |
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Article number | e201800092 |
Number of pages | 18 |
Journal | Life Science Alliance |
Volume | 1 |
Issue number | 3 |
DOIs | |
Publication status | Published - 18 Jun 2018 |
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Dive into the research topics of 'DHX15 regulates CMTR1-dependent gene expression and cell proliferation'. Together they form a unique fingerprint.Projects
- 3 Finished
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Investigating MRNA Methyl Cap Regulation, Function and Therapeutic Potential (Senior Non-Clinical Fellowship)
Cowling, V. (Investigator)
1/01/14 → 31/12/21
Project: Research
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Strategic Award: Wellcome Trust Technology Platform
Blow, J. (Investigator), Lamond, A. (Investigator) & Owen-Hughes, T. (Investigator)
1/01/13 → 30/09/18
Project: Research
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Dynamics of Fundamental Cellular Processes by Live Cell and Tissue Imaging
MacDonald, M. (Investigator), McGloin, D. (Investigator), McKenna, S. (Investigator), Storey, K. (Investigator), Swedlow, J. (Investigator) & Weijer, K. (Investigator)
1/01/13 → 31/12/17
Project: Research
Profiles
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Cowling, Victoria
- Molecular Cell and Developmental Biology - Associate Staff of Biology
Person: Associate Staff