Spliceosomal fidelity

Pre-messenger RNA (pre-mRNA) splicing is an integral step in gene expression, removing introns that would otherwise disrupt the coding potential of gene transcripts. As published in the August 15th issue of G&D, Drs. Tommaso Villa and Christine Guthrie at UCSF have identified a novel splicing fidelity factor, as well as provide additional evidence for a two-step model of pre-mRNA splicing.

The researchers found that deletion of the yeast gene ISY1 reduces the efficiency of the first step of the splicing reaction and decreases 3’-splice site accuracy. Dr. Villa and Guthrie believe that Isy1p interacts with the ATPase Prp16p to regulate spliceosomal conformation, and thereby the fidelity of pre-mRNA splicing.

Dr. Guthrie explains that “15 years ago we hypothesized that the ATPase Prp16 acted as a proofreading clock to limit errors in splicing; the isolation of a Prp16 antagonist (Isy1) provides critical validation for this model and identifies an unexpected fidelity factor.”