Conserved functions of human Pelota in mRNA quality control of nonstop mRNA

FEBS Lett. 2016 Sep;590(18):3254-63. doi: 10.1002/1873-3468.12366. Epub 2016 Sep 7.

Abstract

Dom34-Hbs1 plays crucial roles in Nonstop Decay (NSD) and No-Go Decay (NGD). Here, we report a conserved function of human Pelota (hPelota) in mRNA quality control of nonstop mRNA. hPelota facilitated the expression of the nonstop products from GFP-Rz mRNA, which lacks a termination codon and a poly(A) tail, in exosome-defective mutant cells. hPelota promoted the dissociation of stalled ribosomes at the 3' end of GFP-Rz mRNA, and mutations in domain A diminished this activity. The hPelota-R45A mutant associated with ribosomes but was defective in peptide release. Finally, hPelota promoted the degradation of GFP-Rz mRNA and suppressed the sequential endonucleolytic cleavages caused by stalled ribosomes at the 3' end of mRNA in dom34∆ mutant cells.

Keywords: Pelota; mRNA quality control; nonstop decay; stalled ribosomes.

Publication types

  • Letter

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Codon, Terminator / genetics
  • Drosophila / genetics
  • Endonucleases
  • Endoribonucleases / genetics
  • Exosomes / metabolism
  • HEK293 Cells
  • Humans
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Mutation, Missense
  • Nonsense Mediated mRNA Decay*
  • Nuclear Proteins
  • Protein Binding
  • Protein Domains
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics

Substances

  • Cell Cycle Proteins
  • Codon, Terminator
  • Microfilament Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Dom34 protein, S cerevisiae
  • Endonucleases
  • Endoribonucleases
  • pelo protein, human