Global view of pre-mRNA splicing in Saccharomyces cerevisiae

Proteins, the molecules that carry out most cellular functions, are synthesized according to information contained in DNA sequences. Converting information from DNA into a protein requires an intermediate step in which the DNA sequence is copied into a molecule called mRNA. In humans, there is an essential biochemical process called pre-mRNA splicing, in which certain (non-coding) portions of the sequence are removed and the remaining protein-coding portions are joined together to form a template for protein synthesis. This is a complex process with multiple steps, and even small errors can be dangerous. Many diseases, such as some cancers, Alzheimer's disease, and Parkinson's syndrome, can be attributed to defects in the pre-mRNA splicing machinery. Perhaps due to the complexity and requirement for absolute precision in splicing, the molecular machine that carries out splicing – termed the spliceosome – is enormous. For both humans and yeast, its components number well over 100. However, several splicing proteins likely remain unidentified. A thorough understanding of splicing will require a complete inventory of its parts. Paul Kahlke is identifying novel splicing factors in yeast, which serves as a laboratory model for human splicing. His objective is to uncover previously unknown splicing factors and to determine whether existing candidate proteins are indeed integral to splicing. His studies take a whole genome approach, testing many genes one by one to see which ones are involved in splicing. By screening a large number of genes, Kahlke hopes to identify several new splicing factors and gain insight into the function of known pre-mRNA splicing factors.