Identification of a regulated pathway for nuclear pre-mRNA turnover.
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.
Bousquet-Antonelli
C
C
Wellcome Trust Centre for Cell Biology ICMB, University of Edinburgh, Scotland.
Presutti
C
C
Tollervey
D
D
D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism; D063326:Exosome Multienzyme Ribonuclease Complex; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D008322:Mammals; D009154:Mutation / Q000502:physiology; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D015003:Yeasts / Q000235:genetics*
D005656:Fungal Proteins; D012322:RNA Precursors; C111978:SKI6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C075577:RAT1 protein, S cerevisiae; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex