title: c-Myc co-ordinates mRNA cap methylation and ribosomal RNA production.
abstract: The mRNA cap is a structure added to RNA pol II transcripts in eukaryotes, which recruits factors involved in RNA processing, nuclear export and translation initiation. RNA guanine-7 methyltransferase (RNMT)-RNA-activating miniprotein (RAM), the mRNA cap methyltransferase complex, completes the basic functional mRNA cap structure, cap 0, by methylating the cap guanosine. Here, we report that RNMT-RAM co-ordinates mRNA processing with ribosome production. Suppression of RNMT-RAM reduces synthesis of the 45S ribosomal RNA (rRNA) precursor. RNMT-RAM is required for c-Myc expression, a major regulator of RNA pol I, which synthesises 45S rRNA. Constitutive expression of c-Myc restores rRNA synthesis when RNMT-RAM is suppressed, indicating that RNMT-RAM controls rRNA production predominantly by controlling c-Myc expression. We report that RNMT-RAM is recruited to the ribosomal DNA locus, which may contribute to rRNA synthesis in certain contexts.
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
authors.forename: Sianadh
authors.initials: S
authors.lastname: Dunn
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
authors.forename: Olivia
authors.initials: O
authors.lastname: Lombardi
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
authors.forename: Victoria H
authors.initials: VH
authors.lastname: Cowling
mesh_terms: D002467:Cell Nucleus; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012315:RNA Caps / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012318:RNA Polymerase I / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D016271:Proto-Oncogene Proteins c-myc; D012315:RNA Caps; D012333:RNA, Messenger; D012335:RNA, Ribosomal; C088179:RNA, ribosomal, 45S; D016601:RNA-Binding Proteins; D008780:Methyltransferases; C569288:RAMAC protein, human; C055097:mRNA (guanine(N7))-methyltransferase; D012319:RNA Polymerase II; D012318:RNA Polymerase I
keywords: RNA; RNA pol I; eukaryotic gene expression; mRNA cap