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)

Research output: Contribution to journalArticle

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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

Fingerprint

Cell proliferation
Gene expression
gene expression
RNA
cell proliferation
RNA Polymerase II
Cell Proliferation
Ribosomes
Gene Expression
Messenger RNA
ribosomes
RNA Helicases
Ribose
Protein Biosynthesis
RNA helicases
Transferases
Innate Immunity
Serine
Methylation
ribose

Cite this

Inesta-Vaquera, Francisco ; Chaugule, Viduth K. ; Galloway, Alison ; Chandler, Laurel ; Rojas-Fernandez, Alejandro ; Weidlich, Simone ; Peggie, Mark ; Cowling, Victoria. / DHX15 regulates CMTR1-dependent gene expression and cell proliferation. In: Life Science Alliance. 2018 ; Vol. 1, No. 3.
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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.",
author = "Francisco Inesta-Vaquera and Chaugule, {Viduth K.} and Alison Galloway and Laurel Chandler and Alejandro Rojas-Fernandez and Simone Weidlich and Mark Peggie and Victoria Cowling",
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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 journalArticle

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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

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PY - 2018/6/18

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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.

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