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Regulation and function of CMTR1‐dependent mRNA cap methylation

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mRNA is modified co‐transcriptionally at the 5′ end by the addition of an inverted guanosine cap structure which can be methylated at several positions. The mRNA cap recruits proteins involved in gene expression and identifies the transcript as being cellular or ‘self’ in the innate immune response. Methylation of the first transcribed nucleotide on the ribose 2′‐O position is a prevalent cap modification which has roles in splicing, translation and provides protection against the innate immune response. In this review, we discuss the regulation and function of CMTR1, the first transcribed nucleotide ribose 2′‐O methyltransferase, and the molecular interactions which mediate methylated 2′‐O ribose function. WIREs RNA 2017, 8:e1450. doi: 10.1002/wrna.1450

This article is categorized under:

  • RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
  • RNA Processing > Capping and 5' End Modifications
  • RNA in Disease and Development > RNA in Disease
CMTR1 functional domains. NLS, nuclear localization signal; G‐patch, glycine rich domain; RFM, Rossman‐fold methyltransferase domain; GT‐like, guanylyltransferase‐like domain; WW, protein interaction domain; phos, amino acid 28–66 multiple phosphorylation sites (sites with more than five references in phosphosite plus).
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‘Self’‐RNA recognition and immune tolerence to 2′‐O methylated RNA. CMTR1 and viral methyltransferases (Mtases) catalyse first nucleotide ribose 2′‐O methylation, which prevents transcript recognition by RIG‐I or MDA5. In the absence of ribose 2′‐O methylation, RIG‐I or MDA5 elicit the interferon response which includes expression of IFIT proteins. IFIT1 binds to transcripts unmethylated on ribose 2′‐O to inhibit translation. m7GpppN, 7′‐N cap (N, first nucleotide); m, ribose 2′‐O methylation; Green lines, activity or permissive effect; Black line, binding and repression; Grey dotted lines, absence of translation.
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RNA Processing > Capping and 5′ End Modifications
RNA in Disease and Development > RNA in Disease
RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications

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