The Shuttling Protein Npl3 Promotes Translation Termination Accuracy in Saccharomyces Cerevisiae

J Mol Biol. 2009 Dec 4;394(3):410-22. doi: 10.1016/j.jmb.2009.08.067. Epub 2009 Sep 3.

Abstract

Heterogeneous nuclear ribonucleoproteins are multifunctional proteins that bind to newly synthesized mRNAs in the nucleus and participate in many subsequent steps of gene expression. A well-studied Saccharomyces cerevisiae heterogeneous nuclear ribonucleoprotein that has several nuclear functions is Npl3p. Here, we provide evidence that Npl3p also has a cytoplasmic role: it functions in translation termination fidelity. Yeast harboring the npl3-95 mutant allele have an impaired ability to translate lacZ, enhanced sensitivity to cycloheximide and paromomycin, and increased ability to read through translation termination codons. Most of these defects are enhanced in yeast that also lack Upf1p, an RNA surveillance factor crucial for translation termination. We show that the npl3-95 mutant allele encodes a form of Npl3p that is part of high molecular-weight complexes that cofractionate with the poly(A)-binding protein Pab1p. Together, these results lead us to propose a model in which Npl3p engenders translational fidelity by promoting the remodeling of mRNPs during translation termination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genes, Fungal
  • Kinetics
  • Models, Biological
  • Multiprotein Complexes
  • Mutation
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism*
  • Peptide Chain Termination, Translational*
  • Poly(A)-Binding Proteins / metabolism
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA Helicases / genetics
  • RNA Helicases / metabolism
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Ribonucleoproteins / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Multiprotein Complexes
  • NPL3 protein, S cerevisiae
  • Nuclear Proteins
  • Poly(A)-Binding Proteins
  • RNA, Fungal
  • RNA, Messenger
  • RNA-Binding Proteins
  • Repressor Proteins
  • Ribonucleoproteins
  • Saccharomyces cerevisiae Proteins
  • messenger ribonucleoprotein
  • pab1 protein, S cerevisiae
  • HMT1 protein, S cerevisiae
  • Protein-Arginine N-Methyltransferases
  • SKY1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • NAM7 protein, S cerevisiae
  • RNA Helicases