The Role of Arginine Methylation in Yeast Gene Expression
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The post translation modification of proteins provides the cell with a mechanism to greatly expand the proteomic repertoire and regulate the cell without having to increase it's genetic content. One type of post-translational modification is called arginine methylation. This modification is catalyzed by family of enzymes called Protein Arginine Methyltransferases, or PRMTs. Arginine methylation has roles in the regulation of transcription, RNA processing and DNA damage response pathways. In Saccharomyces cerevisiaethe major PRMT, called Hmt1 has roles in transcriptional silencing and regulation of messenger ribonucleoprotein particle (mRNP) dynamics. To date, there is a lack of knowledge relating to Hmt1's role in transcriptional regulation as compared to PRMTs in metazoans. In this work I have aimed to expand our knowledge of Hmt1's potential roles in transcriptional regulation. We first set out to identify new interactions between Hmt1 and chromatin related genes using Synthetic Genetic Array methodologies. This screen uncovered interactions between Hmt1 and many genes, which are apart of the SAGA, Rpd3-L and Swi/Snf complex, all of which are chromatin-modifying complexes. We found that Hmt1 regulates Rpd3's recruitment to the telomere, and that this resulted in changes in specific histone acetylation levels. The regulation of Rpd3 by Hmt1 also appears to be the mechanism by which Hmt1 regulates silencing. Secondly, we comprehensively mapped Hmt1's interaction with genome. Interestingly we found that Hmt1 occupies a large number of ncRNA genes (tRNAs and snoRNAs). Furthermore, we found that loss of Hmt1 results in an increase in tRNA abundance. We found that Hmt1 interacts with a few components of the core RNAPIII machinery, Bdp1 and Rpc31, the latter being a substrate of Hmt1. Overall, we have expanded our working knowledge of Hmt1's interactions with the chromatin and chromatin related processes, all of which have set the stage for future mechanistic studies.