Molecular Recognition in Biological Systems and Bioinformatics

Protein arginine methylation; genomics; gene expression.

A majority of cellular proteins undergo post-translational modifications. The purpose of these modifications is to serve as cellular molecular switches and to increase proteomic repertoire of a cell. Recently, protein arginine methylation has emerged as a major regulator of protein function. This modification is catalyzed by a family of evolutionarily conserved enzymes called protein arginine methyltransferase (PRMT). In mammalian cells, nine PRMTs and a number of in vivo substrates have been identified thus far. In metazoans, arginine methylation has been shown to be important in the differentiation and development as well as human diseases such as multiple sclerosis, spinal muscular atrophy, and cancer. At the cellular level, this modification affects intracellular protein transport, signal transduction, RNA-processing, and transcription.

Using both yeast and mammalian cells as model organisms, my research is focused on understanding the biological functions of protein arginine methylation at the molecular level using cell biological, biochemistry, and genomics approaches. We are also interested in developing high-throughput technologies that will allow us to rapidly screen and identify PRMT substrates.

Rosetta Resolver Genomics Software

S. cerevisiae, mouse

Hmt1, PRMT6, TREX complex

Cancer, cardiovascular diseases, Fragile X, spinal muscular atrophy, multiple sclerosis, aging

ChIP, ChIP-chip, PCR, protein purifications, molecular biology techniques, RNA techniques, tissue culture, microscopy

Mouse EML-C1 (stem cells)

Moore, M.J., Schwartzfarb, E.M., Silver, P.A., and Yu, M.C. (2006) "Differential recruitment of the splicing machinery during transcription predicts genome-wide patterns of mRNA splicing" Molecular Cell 24(6):903-15

Yu, M.C., Lamming, D.W., Eskin, J.A., Sinclair, D.A., and Silver, P.A. (2006) "The role of protein arginine methylation in the formation of silent chromatin" Genes & Dev. 20(23):3249-3254

Tsankov, A., Brown, C.R., Yu, M.C., Win, M., Silver, P.A., and Casolari, J.M. (2006) "Communication between levels of transcriptional control improves robustness and adaptivity" Mol Syst Biol. 2:65

Yu, M.C., Bachand, F., McBride, A.E., Komili, S., Casolari, J.M., and Silver, P.A. (2004) "Arginine methyltransferase affects interaction and recruitment of mRNA processing and export factors" Genes & Dev. 18(16):2024-35

Hieronymus, H., Yu, M.C., and Silver, P.A. (2004) "mRNA surveillance is coupled to mRNA export" Genes & Dev. 18(21):2652-62