Identification of a regulated pathway for nuclear pre-mRNA turnover

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