Autoregulation of the mRNA export factor Yra1p requires inefficient splicing of its pre-mRNA.

Yra1p is an essential RNA-binding protein that couples transcription to export. The YRA1 gene is one of only approximately 5% of genes that undergo splicing in budding yeast, and its intron is unusual in several respects, including its large size and anomalous branchpoint sequence. We showed previously that the intron is required for autogenous regulation of Yra1p levels, which cause a dominant negative growth phenotype when elevated. The mechanism of this regulation, however, remains unknown. Here we demonstrate that growth is inversely correlated with splicing efficiency. Substitution of a canonical branchpoint moderately improves splicing but compromises autoregulation. Shortening the intron from 766 to approximately 350 nt significantly improves splicing but abolishes autoregulation. Notably, proper regulation can be restored by insertion of unrelated sequences into the shortened intron. In that the current paradigm for regulated splicing involves the binding of protein factors to specific elements in the pre-mRNA, the regulation of YRA1 expression appears to occur by a novel mechanism. We propose that appropriate levels of Yra1p are maintained by inefficient cotranscriptional splicing.