Nuclear Retention of Unspliced mRNAs in Yeast Is Mediated by Perinuclear Mlp1

Cell. 2004 Jan 9;116(1):63-73. doi: 10.1016/s0092-8674(03)01026-2.

Abstract

The molecular mechanism underlying the retention of intron-containing mRNAs in the nucleus is not understood. Here, we show that retention of intron-containing mRNAs in yeast is mediated by perinuclearly located Mlp1. Deletion of MLP1 impairs retention while having no effect on mRNA splicing. The Mlp1-dependent leakage of intron-containing RNAs is increased in presence of ts-prp18 delta, a splicing mutant. When overall pre-mRNA levels are increased by deletion of RRP6, a nuclear exosome component, MLP1 deletion augments leakage of only the intron-containing portion of mRNAs. Our data suggest, moreover, that Mlp1-dependent retention is mediated via the 5' splice site. Intriguingly, we found Mlp-proteins to be present only on sections of the NE adjacent to chromatin. We propose that at this confined site the perinuclear Mlp1 implements a quality control step prior to export, physically retaining faulty pre-mRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Cell Nucleus / genetics*
  • Cell Nucleus / metabolism
  • Exoribonucleases / deficiency
  • Exoribonucleases / genetics
  • Exosome Multienzyme Ribonuclease Complex
  • Introns / genetics
  • Mutation / genetics
  • Nuclear Envelope / genetics
  • Nuclear Envelope / metabolism
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Protein Transport / genetics
  • RNA Splice Sites / genetics
  • RNA Splicing / genetics*
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins
  • Ribonucleoprotein, U5 Small Nuclear
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Yeasts / genetics*
  • Yeasts / metabolism

Substances

  • MLP1 protein, S cerevisiae
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • PRP18 protein, S cerevisiae
  • RNA Splice Sites
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ribonucleoprotein, U5 Small Nuclear
  • Saccharomyces cerevisiae Proteins
  • Exoribonucleases
  • Exosome Multienzyme Ribonuclease Complex
  • RRP6 protein, S cerevisiae