Overlapping cistrons within mammalian mRNAs

Type of Award: Catalyst
Date Awarded: February 2016
Award End Date: January 2018
Amount Awarded: $ 200,000.00
PI(s): Christopher Gomez, UChicago; Jeffrey Savas, NU;

Abstract: We discovered that the CACNA1A calcium channel gene is actually bi-cistronic, meaning that it can generate two distinct proteins, the calcium channel protein plus a separate transcription factor protein we named 1ACT. This contradicts the "One gene-one polypeptide hypothesis" of Beadle and Tatum (Nobel Prize, 1958). Although exceptions had previously been found, this is the most complete evidence to date for bi-cistronic, protein-encoding vertebrate genes. We have found additional evidence that other ion channel genes contain a second cistron that also encode transcription factors, suggesting a novel gene expression strategy. Curiously mutations of several of these genes leads to complex disease relevant phenotypes, possibly owing to the effect of the mutation on both proteins. We aim to identify the set of bi-cistronic genes that express structural proteins in tandem with transcription factors which inform disease mechanisms.