Identification of a regulated pathway for nuclear pre-mRNA turnover

Cell. 2000 Sep 15;102(6):765-75. doi: 10.1016/s0092-8674(00)00065-9.


We have identified a nuclear pathway that rapidly degrades unspliced pre-mRNAs in yeast. This involves 3'-->5' degradation by the exosome complex and 5'-->3' degradation by the exonuclease Rat1p. 3'-->5' degradation is normally the major pathway and is regulated in response to carbon source. Inhibition of pre-mRNA degradation resulted in increased levels of pre-mRNAs and spliced mRNAs. When splicing was inhibited by mutation of a splicing factor, inhibition of turnover resulted in 20- to 50-fold accumulation of pre-mRNAs, accompanied by increased mRNA production. Splicing of a reporter construct with a 3' splice site mutation was also increased on inhibition of turnover, showing competition between degradation and splicing. We propose that nuclear pre-mRNA turnover represents a novel step in the regulation of gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / enzymology
  • Cell Nucleus / genetics
  • Exoribonucleases / genetics
  • Exoribonucleases / metabolism
  • Exosome Multienzyme Ribonuclease Complex
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Genotype
  • Mammals
  • Mutation / physiology
  • RNA Precursors / metabolism*
  • RNA Splicing / physiology*
  • Saccharomyces cerevisiae Proteins*
  • Yeasts / genetics*


  • Fungal Proteins
  • RNA Precursors
  • SKI6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • RAT1 protein, S cerevisiae
  • Exoribonucleases
  • Exosome Multienzyme Ribonuclease Complex