Pre-mRNA splicing, the removal of noncoding intron sequences from pre-messenger RNA, is carried out by the spliceosome, a dynamic ribonucleoprotein complex that assembles onto pre-mRNA co-transcriptionally, and is functionally conserved across eukaryotes. Splicing regulation provides an elegant mechanism for controlling the expression of genes required for key cellular processes.
Despite its relatively streamlined genome, there are important examples of regulated RNA splicing in Saccharomyces cerevisiae that reveal fundamental mechanistic insights. One of the most striking is the regulated splicing of meiotic transcripts. When cells experience nitrogen starvation and in the presence of a poor carbon source, diploid yeast cells undergo meiosis and package the resulting haploid nuclei into spores. This involves a dramatic reprogramming of gene expression, including regulated splicing of a number of RNAs that are only expressed during meiosis. Studies will be presented that describe a crucial role for the chromatin-remodeling complex Swi/Snf in meiotic regulation of splicing—by several unexpected mechanisms.
These observations have led us to explore other ways in which splicing regulation controls nutrient response. The transcription factor Gcr1 (GlyColysis regulator 1) controls expression of over 75% of the genes in actively growing yeast. GCR1 RNA contains a highly conserved intron, which allows the cell to generate multiple RNA isoforms whose levels and ratios change upon glucose depletion. The protein isoforms resulting from translation of the alternatively spliced RNAs play crucial roles in the cell’s ability to adjust its metabolic program in response to environmental change. (Hossain et al. Molecular Cell 2016). These studies have yielded new insights into mechanisms of regulated splicing and its impact on downstream processing events, which will be described.
Taken together, this work reveals the intricate connection between RNA splicing, transcription, and chromatin modification. Moreover, these mechanisms uncover key insights into splicing regulation across eukaryotes.