Hypermethylated-capped selenoprotein mRNAs in mammals

Nucleic Acids Res. 2014 Jul;42(13):8663-77. doi: 10.1093/nar/gku580. Epub 2014 Jul 10.

Abstract

Mammalian mRNAs are generated by complex and coordinated biogenesis pathways and acquire 5'-end m(7)G caps that play fundamental roles in processing and translation. Here we show that several selenoprotein mRNAs are not recognized efficiently by translation initiation factor eIF4E because they bear a hypermethylated cap. This cap modification is acquired via a 5'-end maturation pathway similar to that of the small nucle(ol)ar RNAs (sn- and snoRNAs). Our findings also establish that the trimethylguanosine synthase 1 (Tgs1) interacts with selenoprotein mRNAs for cap hypermethylation and that assembly chaperones and core proteins devoted to sn- and snoRNP maturation contribute to recruiting Tgs1 to selenoprotein mRNPs. We further demonstrate that the hypermethylated-capped selenoprotein mRNAs localize to the cytoplasm, are associated with polysomes and thus translated. Moreover, we found that the activity of Tgs1, but not of eIF4E, is required for the synthesis of the GPx1 selenoprotein in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Eukaryotic Initiation Factor-4E / metabolism
  • Glutathione Peroxidase / biosynthesis
  • Glutathione Peroxidase / genetics
  • Humans
  • Methylation
  • Methyltransferases / metabolism
  • Nuclear Proteins / metabolism
  • Polyribosomes / chemistry
  • Protein Biosynthesis
  • RNA Caps / metabolism*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism
  • Ribonucleoproteins, Small Nucleolar / metabolism
  • SMN Complex Proteins / metabolism
  • Selenoproteins / biosynthesis
  • Selenoproteins / genetics*
  • Selenoproteins / metabolism

Substances

  • Eukaryotic Initiation Factor-4E
  • NOP58 protein, human
  • Nuclear Proteins
  • RNA Caps
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ribonucleoproteins, Small Nucleolar
  • SECISBP2 protein, human
  • SMN Complex Proteins
  • Selenoproteins
  • glutathione peroxidase GPX1
  • Glutathione Peroxidase
  • Methyltransferases
  • trimethylguanosine synthase

Associated data

  • GEO/GSE57625