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Biological Functions of Protein Arginine Methylation

Protein arginine methylation has recently emerged as a major regulator of protein functions in eukaryotic cells. This post-translational modification is catalyzed by a family of enzymes called protein arginine methyltransferase (PRMT). In mammalian cells, there are currently nine PRMTs that have been identified. Nevertheless, much of their true in vivo substrates remain to be discovered.

Our lab is interested in understanding the role of this modification on the function of methylated-substrates. There are three main areas of research:

The Role of Protein Arginine Methylation in mRNP dynamics

Eukaryotic pre-mRNA processing events occur co-transcriptionally and many components of the machineries responsible for these reactions are substrates of PRMTs. Using yeast as a model organism, our data demonstrated a role for Hmt1 in modulating proper co-transcriptional recruitment of RNA processing factors. Nevertheless, detailed mechanism by which this occurs remain to be investigated.

Transcriptional Regulation by Protein Arginine Methylation

Protein arginine methylation has been implicated in regulating aspects of transcription. For example, arginine methylation of histones provided positive or negative mark in transcriptional activation. Methylation of components of transcriptional machinery such as Spt5 and PGC-1α by PRMTs is critical for their biological function. To better understand the role of protein arginine methylation in transcriptional activation/repression, we are using a systems biology strategy that encompasses genomic, genetic, and proteomic approaches to identify novel regulatory functions for PRMTs in transcription.

The Role of PRMTs in Stem Cell Function

Unlike normal somatic cells, embryonic stem cells can proliferate indefinitely in culture where they do not appear to undergo senescence and yet remain untransformed. Recent studies have shown that stem cells’ capacity in combating genome instability contributes to its stemness and its lack of senescence. The physiological consequence of genome instability is uncontrolled cell division or inhibition of programmed cell death. Thus, studying how stem cells regulate their capacity in preserving genome integrity can enhance our ability to devise strategies that will help realize the therapeutic potential of stem cells in human diseases. In addition, it will allow us to better understand the fundamental biology governing stem cell function and development.