Identification of a Regulated Pathway for Nuclear Pre-mRNA Turnover

• Published in: Cell Vol. 102; no. 6; pp. 765 - 775
• Main Authors: Bousquet-Antonelli, Cécile, Presutti, Carlo, Tollervey, David
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-09-2000
• Subjects: Animals; Cell Nucleus - enzymology; Cell Nucleus - genetics; Exoribonucleases - genetics; Exoribonucleases - metabolism; Exosome Multienzyme Ribonuclease Complex; Fungal Proteins - genetics; Fungal Proteins - metabolism; Genotype; Mammals; mRNA turnover; Mutation - physiology; RNA Precursors - metabolism; RNA Splicing - physiology; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Yeasts - genetics
• ISSN: 0092-8674; 1097-4172
• 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.