Michael C. Yu

PhD

Michael C. Yu.

Michael C. Yu

PhD

Michael C. Yu

PhD

Research Interests

Biological functions of protein methylation

Contact Information

C509 Cooke Hall

Buffalo NY, 14260

Phone: (716) 645-4931

mcyu@buffalo.edu

Education

  • PhD, University of California, Los Angeles
  • Postdoctoral Research, Harvard Medical School

Office Hours

  • BIO 319 Course: Tuesday 11-12pm or by appointment.
  • BIO 332 and BIO 404/504 Course: By appointment.

Research Summary

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 enzyme called protein arginine methyltransferase (PRMT).  In the metazoans, protein arginine methylation has been shown to play a role in the differentiation and development as well as etiology of human diseases such as multiple sclerosis, spinal muscular atrophy, and cancer.  Using both yeast and mammalian cells as model organisms, my lab is focused on understanding the biological functions of protein arginine methylation at the molecular level using cell biological, biochemistry, proteomics, and genomics approaches.

The Role of Protein Arginine Methylation in pre-mRNA Splicing
In eukaryotes, pre-mRNA splicing is a process by which intronic sequences are precisely removed from pre-mRNAs.  This process is critical to ensure proper gene expression.  Pre-mRNA splicing is carried out by the spliceosome, a large molecular machine composed of five small nuclear ribonucleoprotein complexes (snRNPs) and scores of associated factors. Many spliceosomal and associated proteins are subject to regulation via post-translational modifications such as methylation and phosphorylation.  Although the role of phosphorylation has been widely examined, far less is known about mechanisms by which methylation impacts pre-mRNA splicing, despite of our ever-increasing awareness of the importance of this post-translational modification in other facets of biology such as chromatin function.  As such, elucidating how methylation affects the molecular interactions that are key to the creation of a properly functioning spliceosome will significantly advance our understanding of splicing regulation.  Previous work from my lab has established a critical role for protein arginine methylation in pre-mRNA splicing, wherein it functions by an as yet poorly understood mechanism to control co-transcriptional recruitment of spliceosomal and associated proteins to nascent pre-mRNA molecules.  Building upon these findings, my lab is interested in defining the molecular basis by which this critical regulatory step is manifested.

Modulation of RNA Pol III Transcription by Protein Arginine Methylation
Within the cell, RNA polymerase III (Pol III) is responsible for the production of small, untranslated structural RNAs for protein synthesis.  These include the 5S rRNA and tRNA, which are highly abundant and account for approximately 15% of total cellular RNA by weight.  Regulating the biogenesis of these small RNAs is important, as the availability of components of the protein synthesis apparatus is a determinant of a cell’s biosynthesis capacity and must be produced in high quantity to fulfill the cell’s biosynthetic demand during growth.  Recently, we defined a role for PRMT1 in controlling transcription by RNA Pol III.   In budding yeast, we used a genomic approach to uncover an enrichment of yeast PRMT1 (termed Hmt1) occupancy at tRNA genes and physical association of Hmt1 with RNA Pol III transcription factors.  A change in the level of precursor tRNAs is also observed in Hmt1 loss-of-function mutants, suggesting a role for this enzyme in facilitating the biogenesis of tRNAs.  Our lab is interested in dissecting the molecular basis by which Hmt1 modulates RNA Pol III transcription and in the process, learning how this post-translational modification impacts the biology of tRNA biogenesis.

Science Signaling.

Control of GPCR Signaling by Protein Arginine Methylation
In eukaryotes, G protein-coupled receptors (GPCRs) are the largest and most diverse group of membrane receptors and these receptors play an important role in mediating a variety of physiological responses such as responses to hormones, neurotransmitters, and environmental stimulants. Individual GPCRs have unique combination of signal-transduction activities and understanding the mechanisms that regulate these activities is crucial for designing potential therapeutic strategies. In collaboration with Drs. Denise Ferkey and Stewart Clark here at UB, we have identified arginine methylation as a post-translational modification that contributes to human D2 dopamine receptor function.  Currently, we are interested in elucidating the molecular mechanism by which this modification regulates receptor signaling. 

Selected Publications

  • Davis, R.B., Likhite, N., Jackson, C.A., Liu, T., and Yu, M.C. (2019) Robust repression of tRNA gene transcription during stress requires protein arginine methylation.  Life Sci. Alliance. 2019 Jun;2(3). PMID: 31160378.
  • Bowitch, A., Michaels, K.L., Yu, M.C. and Ferkey, D.M. (2018) The Protein Arginine Methyltransferase PRMT-5 regulates SER-2 Tyramine Receptor-mediated Behaviors in C. elegansG3: Genes, Genomes, Genetics. 8(7):2389-2398. Article.
  • Banerjee R, Rudloff Z, Naylor C, Yu M, Gunawardena S. (2018) The Presenilin Loop Region is Essential for Glycogen Synthase Kinase 3 beta Mediated Functions on Motor Proteins During Axonal Transport.  Hum Mol Genet. 2018 May 22. doi: 10.1093/hmg/ddy190.
  • Muddukrishna, B., Jackson, C.A. and Yu, M.C.  (2017)  Protein Arginine Methylation of Npl3 Promotes Splicing of the SUS1 Intron Harboring Non-Consensus 5′ Splice Site and Branch Site.  Biochim Biophys Acta (BBA) – Gene Regulatory Mechanisms.  1860(6):730-739.
  • Likhite, N., Jackson, C.A., Liang, M-S., Krzyzanowski, M.C., Lei, P., Wood, J.F., Birkaya, B., Michaels, K.L., Andreadis, S.T., Clark, S.D., Yu, M.C. and Ferkey, D.M.  (2015)  The protein arginine methyltransferase PRMT5 regulates D2-like dopamine receptor signaling.  Science Signaling.  8(402):ra115.
  • Jackson, C.A. and Yu, M.C.  (2014)  Detection of Protein Arginine Methylation in Saccharomyces cerevisiae.  Methods Mol. Biol.  1163:229-47.
  • Krzyzanowski, M.C., Ezak, M.J., Brueggemann, C., Wood, J.F., Michaels, K.L., Jackson, C.A., Collins, K.D., Yu, M.C., L’Etoile, N.D., and Ferkey, D.M.  (2013)  The C. elegans cGMP-dependent Protein Kinase EGL-4 Regulates Nociceptive Behavioral Sensitivity.   PLoS Genetics.  Jul;9(7):e1003619.
  • Milliman, E.J., Hu, Z., and Yu, M.C.  (2012)  Genomic Insights of Protein Arginine Methyltransferase Hmt1 Binding Reveals Novel Regulatory Functions. BMC Genomics.13(1):728.
  • Jackson, C.J., Yadav, N., Min, S., Li, J., Milliman, E.J., Qu, J., Chen, Y-C., and Yu, M.C.  (2012) Proteomic Analysis of Interactors for Yeast Protein Arginine Methyltransferase Hmt1 Reveals Novel Substrate and Insights into Additional Biological Roles.   Proteomics.  Sep 20. doi:10.1002/pmic.201200132.
  • Milliman, E.J., Yadav, N., Chen, Y-C., Muddukrishna, B., Karunanithi, S., and Yu, M.C.  (2012) Recruitment of Rpd3 to the Telomere Depends on the Protein Arginine Methyltransferase Hmt1. PLoS ONE 7(8):e44656.
  • Yu, M.C. (2011) The Role of Protein Arginine Methylation in mRNP Dynamics. Mol. Biol. Int. 2011:16382
  • Chen, Y-C., Milliman, E.J., Goullet, I., Cote, J.,  Vollbracht, J.A., and Yu, M.C.  (2010)  Protein Arginine Methylation Facilitates Co-transcriptional Recruitment of Pre-mRNA Splicing Factors.  Mol. Cell. Biol.  30(21):5245-56.
  • Hoke, S.M., Mutiu, I.A., Genereaux, J., Kvas, S., Buck, M., Yu, M.C., Gloor, G.B., and Brandl, C.J. (2010)  Mutational Analysis of the C-terminal FATC Domain of Saccharomyces cerevisiae Tra1.  Curr. Genet.  56(5):447-65.
  • 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.  Mol. Cell. 24(6):903-15.
            * Article was highlighted by a Faculty of 1000 “Must Read” rating
  • 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
    • Article was highlighted by News & Views in Nat. Struct. Mol. Biol (2004) Oct; 11(10):914-5.
    • Article was highlighted by a Faculty of 1000 “Recommended” rating.
  • Hieronymus, H., Yu, M.C., and Silver, P.A. (2004) mRNA Surveillance is Coupled to mRNA export.  Genes Dev. 18(21):2652-62.