The coding regions of most eukaryotic genes are interrupted by non-coding introns which must be removed from the pre-mRNA prior to translation. We are taking genome-wide approaches to (1) identify the different conditions under which this process is used as a control point for regulating gene exp...
The coding regions of most eukaryotic genes are interrupted by non-coding introns which must be removed from the pre-mRNA prior to translation. We are taking genome-wide approaches to (1) identify the different conditions under which this process is used as a control point for regulating gene expression, and (2) determine the mechanisms by which this control is manifested. During my post-doctoral work, prior to my arrival at Cornell, I developed microarrays that allowed me to examine pre-mRNA splicing from a genome-wide perspective in the budding yeast, Saccharomyces cerevisiae. The yeast genome is relatively devoid of introns, containing only ~ 300 introns in its ~6000 genes (the human genome, by comparison, has over 250,000 introns). Furthermore, yeast appeared to lack many of the features associated with alternative splicing in higher systems. As such, it had previously been widely believed that yeast lacked the capacity to regulate pre-mRNA splicing in a transcript specific fashion. However, by systematically examining the global changes in pre-mRNA splicing in response to changing environmental conditions, I was able to demonstrate that this process could be utilized as an important regulatory control point. This important finding demonstrates that mechanisms exist by which changes in external environment can be sensed by the organism and can lead to rapid and specific changes in the activity of this process. We are now aggressively examining how widely this regulatory paradigm is used, as well as its mechanistic underpinnings. In addition to our work in budding yeast, we are expanding this work into organisms with more complex intron architecture, including the fission yeast Schizosaccharomyces pombe.