SECIS-binding protein 2 interacts with the SMN complex and the methylosome for selenoprotein mRNP assembly and translation

Nucleic Acids Res. 2017 May 19;45(9):5399-5413. doi: 10.1093/nar/gkx031.

Abstract

Selenoprotein synthesis requires the co-translational recoding of a UGASec codon. This process involves an RNA structural element, called Selenocysteine Insertion Sequence (SECIS) and the SECIS binding protein 2 (SBP2). Several selenoprotein mRNAs undergo unusual cap hypermethylation by the trimethylguanosine synthase 1 (Tgs1), which is recruited by the ubiquitous Survival of MotoNeurons (SMN) protein. SMN, the protein involved in spinal muscular atrophy, is part of a chaperone complex that collaborates with the methylosome for RNP assembly. Here, we analyze the role of individual SMN and methylosome components in selenoprotein mRNP assembly and translation. We show that SBP2 interacts directly with four proteins of the SMN complex and the methylosome core proteins. Nevertheless, SBP2 is not a methylation substrate of the methylosome. We found that both SMN and methylosome complexes are required for efficient translation of the selenoprotein GPx1 in vivo. We establish that the steady-state level of several selenoprotein mRNAs, major regulators of oxidative stress damage in neurons, is specifically reduced in the spinal cord of SMN-deficient mice and that cap hypermethylation of GPx1 mRNA is affected. Altogether we identified a new function of the SMN complex and the methylosome in selenoprotein mRNP assembly and expression.

MeSH terms

  • Glutathione Peroxidase
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Methylation
  • Models, Biological
  • Muscular Atrophy, Spinal / metabolism
  • Muscular Atrophy, Spinal / pathology
  • Protein Binding
  • Protein Biosynthesis*
  • RNA-Binding Proteins / metabolism*
  • Ribonucleoproteins / metabolism*
  • SMN Complex Proteins / metabolism*
  • Selenoproteins / metabolism*
  • Spinal Cord / metabolism

Substances

  • RNA-Binding Proteins
  • Ribonucleoproteins
  • SECISBP2 protein, human
  • SMN Complex Proteins
  • Selenoproteins
  • messenger ribonucleoprotein
  • glutathione peroxidase GPX1
  • Glutathione Peroxidase