c-Myc co-ordinates mRNA cap methylation and ribosomal RNA production

Biochem J. 2017 Feb 1;474(3):377-384. doi: 10.1042/BCJ20160930. Epub 2016 Dec 1.

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.

Keywords: RNA; RNA pol I; eukaryotic gene expression; mRNA cap.

MeSH terms

  • Cell Nucleus
  • Chromatin / chemistry
  • Chromatin / metabolism
  • HeLa Cells
  • Humans
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Protein Biosynthesis
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA Caps / chemistry*
  • RNA Caps / genetics
  • RNA Caps / metabolism
  • RNA Polymerase I / genetics
  • RNA Polymerase I / metabolism
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA, Ribosomal / genetics
  • RNA, Ribosomal / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Ribosomes / chemistry
  • Ribosomes / metabolism
  • Transcription, Genetic

Substances

  • Chromatin
  • Proto-Oncogene Proteins c-myc
  • RNA Caps
  • RNA, Messenger
  • RNA, Ribosomal
  • RNA, ribosomal, 45S
  • RNA-Binding Proteins
  • Methyltransferases
  • RAMAC protein, human
  • mRNA (guanine(N7))-methyltransferase
  • RNA Polymerase II
  • RNA Polymerase I