Alan Zahler, PhD

Lab Head

Zahler, UC Santa Cruz

Research in our laboratory is focused on the alternative splicing code; the sequences on the pre-mRNA and the protein factors that bind to them which regulate alternative splicing. We have focused on the identification of the cis splicing-regulatory elements, the trans-acting protein factors that bind them, and the mechanisms by which splicing is regulated. Our laboratory is using the powerful genetic, molecular biology and bioinformatics tools available for the nematode Caenorhabditis elegans to tackle this problem. A recent area of focus is the connection between alternative splicing and message stability. In about 1/3 of cases, alternative splicing yields an isoform with a premature stop codon; this isoform is unstable and subject to nonsense-mediated mRNA decay. We have identified many examples of alternative splicing factors whose own expression is regulated by alternative splicing coupled to nonsense-mediated decay. We are characterizing this process in C. elegans where we have uncovered a phenomenon in which the efficiency of nonsense-mediated decay can be developmentally regulated.