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 |
|---|---|
| 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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DHX15 regulates CMTR1-dependent gene expression and cell proliferation. / Inesta-Vaquera, Francisco; Chaugule, Viduth K.; Galloway, Alison; Chandler, Laurel; Rojas-Fernandez, Alejandro; Weidlich, Simone; Peggie, Mark; Cowling, Victoria (Lead / Corresponding author).
In: Life Science Alliance, Vol. 1, No. 3, e201800092, 18.06.2018.Research output: Contribution to journal › Article
TY - JOUR
T1 - DHX15 regulates CMTR1-dependent gene expression and cell proliferation
AU - Inesta-Vaquera, Francisco
AU - Chaugule, Viduth K.
AU - Galloway, Alison
AU - Chandler, Laurel
AU - Rojas-Fernandez, Alejandro
AU - Weidlich, Simone
AU - Peggie, Mark
AU - Cowling, Victoria
N1 - Research funded by MRC Senior Fellowship (VC) MR/K024213/1, Lister Institute Prize Fellowship (VC), Wellcome Trust Technology Platform award 097945/B/11/Z; MRC Next Generation Optical Microscopy award MR/K015869/1.
PY - 2018/6/18
Y1 - 2018/6/18
N2 - 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.
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 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.
U2 - 10.26508/lsa.201800092
DO - 10.26508/lsa.201800092
M3 - Article
C2 - 30079402
VL - 1
JO - Life Science Alliance
JF - Life Science Alliance
SN - 2575-1077
IS - 3
M1 - e201800092
ER -