CMTR1-Catalyzed 2′-O-Ribose Methylation Controls Neuronal Development by Regulating Camk2α Expression Independent of RIG-I Signaling

Lee, Yen-Lurk; Kung, Fan-Che; Lin, Chia‐Hsuan; Huang, Yu-Shan

doi:10.1016/j.celrep.2020.108269

Cited by 24 publications

(28 citation statements)

References 64 publications

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“…As an interferon stimulated gene (ISG), CMTR1 has been found to be important for the expression of a subset of other ISGs ( 20 ). In vivo , CMTR1 is required for neuromorphogenesis and brain development, in particular promoting Camk2a expression ( 21 ). The mechanisms directing these gene-specific impacts of CMTR1 are not known.…”

Section: Introductionmentioning

confidence: 99%

CMTR1 is recruited to transcription start sites and promotes ribosomal protein and histone gene expression in embryonic stem cells

Shang

Silva

Suska

et al. 2022

Nucleic Acids Research

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CMTR1 (cap methyltransferase 1) catalyses methylation of the first transcribed nucleotide of RNAPII transcripts (N1 2′-O-Me), creating part of the mammalian RNA cap structure. In addition to marking RNA as self, N1 2′-O-Me has ill-defined roles in RNA expression and translation. Here, we investigated the gene specificity of CMTR1 and its impact on RNA expression in embryonic stem cells. Using chromatin immunoprecipitation, CMTR1 was found to bind to transcription start sites (TSS) correlating with RNAPII levels, predominantly binding at histone genes and ribosomal protein (RP) genes. Repression of CMTR1 expression resulted in repression of RNAPII binding at the TSS and repression of RNA expression, particularly of histone and RP genes. In correlation with regulation of histones and RP genes, CMTR1 repression resulted in repression of translation and induction of DNA replication stress and damage. Indicating a direct role for CMTR1 in transcription, addition of recombinant CMTR1 to purified nuclei increased transcription of the histone and RP genes. CMTR1 was found to be upregulated during neural differentiation and there was an enhanced requirement for CMTR1 for gene expression and proliferation during this process. We highlight the distinct roles of the cap methyltransferases RNMT and CMTR1 in target gene expression and differentiation.

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Section: Introductionmentioning

confidence: 99%

CMTR1 is recruited to transcription start sites and promotes ribosomal protein and histone gene expression in embryonic stem cells

Shang

Silva

Suska

et al. 2022

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…Notably, immune genes were not significantly up-regulated in the double mutant flies ( Data S1 ) and CMTr1 knock-out mice 34 . Since only a proportion of all mRNAs have cOMe in both Drosophila and mice ( Fig.…”

Section: Resultsmentioning

confidence: 96%

CMTr cap-adjacent 2’-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses

et al. 2021

Preprint

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Cap-adjacent nucleotides of animal, protist and viral mRNAs can be dynamically O-methylated at the 2’ position of the ribose (cOMe). The functions of cOMe in animals, however, remain unknown. Here we show that the two cap methyltransferases (CMTr1 and CMTr2) of Drosophila can methylate the ribose of the first nucleotide in mRNA. Double-mutant flies lack cOMe but are viable. Consistent with prominent neuronal expression, they have a reward learning defect that can be rescued by conditional expression in mushroom body neurons before training. Among CMTr targets are cell adhesion and signaling molecules relevant for learning and cOMe is required for local translation of mRNAs at synapses. Hence, our study reveals a mechanism to co-transcriptionally prime mRNAs by cOMe for localized protein synthesis at synapses.

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“…Thus, we observed that CMTR1 controls RNA levels in a gene specific manner in ESCs, correlating with RNAPII binding and expression level. In neurons, CMTR1 was found to control expression of Camk2a (21), and in the innate immune response, CMTR1 was found to be required for upregulation of certain interferon stimulated genes (20). In both scenarios and presented here in ESCs, CMTR1 is controlling the expression of some of the most highly expressed genes in the cell.…”

Section: Discussionmentioning

confidence: 99%

CMTR1 is recruited to transcription start sites and promotes ribosomal protein and histone gene expression in embryonic stem cells

Shang

Silva

Suska

et al. 2022

Preprint

View full text Add to dashboard Cite

CMTR1 (cap methyltransferase 1) catalyses methylation of the first transcribed nucleotide of RNAPII transcripts (N1 2′-O-Me), creating part of the mammalian RNA cap structure. In addition to marking RNA as self, N1 2′-O-Me has ill-defined roles in RNA expression and translation. Here we investigated the gene specificity of CMTR1 and its impact on RNA expression in embryonic stem cells. Using chromatin immunoprecipitation, CMTR1 was found to bind to transcription start sites (TSS) correlating with RNAPII levels, predominantly binding at histone genes and ribosomal protein (RP) genes. Repression of CMTR1 expression resulted in repression of RNAPII binding at the TSS and repression of RNA expression, particularly of histone and RP genes. In correlation with regulation of histones and RP genes, CMTR1 repression resulted in repression of translation and induction of DNA replication stress and damage. Indicating a direct role for CMTR1 in transcription, addition of recombinant CMTR1 to purified nuclei increased transcription of the histone and RP genes. CMTR1 was found to be upregulated during neural differentiation and there was an enhanced requirement for CMTR1 for gene expression and proliferation during this process. We highlight the distinct roles of the cap methyltransferases RNMT and CMTR1 in target gene expression and differentiation.

show abstract

CMTR1-Catalyzed 2′-O-Ribose Methylation Controls Neuronal Development by Regulating Camk2α Expression Independent of RIG-I Signaling

Cited by 24 publications

References 64 publications

CMTR1 is recruited to transcription start sites and promotes ribosomal protein and histone gene expression in embryonic stem cells

CMTR1 is recruited to transcription start sites and promotes ribosomal protein and histone gene expression in embryonic stem cells

CMTr cap-adjacent 2’-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses

CMTR1 is recruited to transcription start sites and promotes ribosomal protein and histone gene expression in embryonic stem cells

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