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Faculty & Research

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Jeffry Corden

Department Affiliation Primary: Molecular Biology & Genetics
RankProfessor
Phone Numbers410-955-4719
Fax: 410-502-6718
Emailjcorden@jhmi.edu
School of Medicine Address725 N. Wolfe Street
617 Hunterian
Baltimore MD 21205
Link to Lab Homepage
Jeffry Corden

Research Topic: RNA Polymerase II Phosphorylation and Transcription Regulation

Eucaryotic RNA polymerase II is unique among RNA polymerases in containing an unusual repetitive domain at the C-terminus of the largest subunit. This C-terminal domain (CTD) is comprised of tandem repeats of the consensus sequence TyrSerProThrSerProSer. We are using genetic and biochemical approaches to investigate the functional role of the CTD in biogenesis of mRNA. Both yeast and mammalian systems are being employed.

A major effort in the lab is directed at studies of proteins that bind the CTD. Using the yeast two-hybrid approach we identified a family of proteins that interact with the CTD. These proteins are similar to the serine/arginine-rich proteins involved in pre-mRNA splicing. A current focus of the laboratory is to determine how these proteins function in mRNA biogenesis and how CTD phosphorylation regulates this function.

The yeast Nrd1 and Nab3 proteins interact with the CTD and act to direct termination of Pol II transcripts in a manner that does not lead to polyadenylation. We have shown that this pathway is important for formation of the 3’ ends of small nuclear and nucleolar RNA transcripts in yeast. Furthermore, this pathway directs termination of a class of yeast intergenic and antisense transcripts. This surveillance mechanism involves the exonuclease complex called the nuclear exosome and an RNA helicase called Sen1. We are currently investigating the mechanism by which RNA sequences in the nascent transcript trigger Pol II termination. We are also beginning to investigate the role of related human proteins that bind both the CTD and RNA. We have not yet identified the RNA (gene) targets of these proteins and this is a project open to incoming graduate students.

Publications:

Darby M.M., Serebreni L., Pan X., Boeke J.D., Corden J.L. (2012) The S. cerevisiae Nrd1-Nab3 Transcription Termination Pathway Acts in Opposition to Ras Signaling and Mediates Response to Nutrient Depletion.  Mol Cell Biol. 32:1762-75.
PubMed Reference

Jamonnak, N., Creamer, T., Darby, M., Schaughency, P. Wheelan, S., Corden, J. (2011) Yeast Nrd1, Nab3 and Sen1 transcriptome-wide binding maps suggest multiple roles in post-transcriptional RNA processing. RNA 17, 2011-2025.
PubMed Reference

Creamer, T. J., Darby, M.M., Jamonnak, N., Schaughency, P, Hao, H., Wheelan, S.J., Corden, J.L. (2011) Transcriptome-wide binding sites for componenets of the Saccharomyces cerevisiae non-poly(A) termination pathway: Nrd1, Nab3 and Sen1. PLoS Genetics 7, e1002329.
PubMed Reference

Corden JL (2010) Shining a new light on RNA-protein interactions.  Chem Biol 17(4):316-318.
PubMed Reference

Corden JL (2008) Yeast Pol II start-site selection: the long and the short of it. EMBO Rep 9:1084-1086.
PubMed Reference

Corden JL (2007) Transcription. Seven ups the code.  Science 318:1735-1736.
PubMed Reference

Carroll, K. L., Ghirlando, R., Ames, J. M., and Corden, J. L. (2007). Interaction of yeast RNA-binding proteins Nrd1 and Nab3 with RNA polymerase II terminator elements. RNA 13: 361-373.
PubMed Reference​ 

Arigo, J.T., Eyler, D.E., Carroll, K.L., and Corden, J.L. (2006) Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. Mol Cell. 23: 841-851. 
PubMed Reference
 

Arigo, J.T., Carroll, K.L., Ames, J.M., and Corden, J.L. (2006) Regulation of yeast NRD1 expression by premature transcription termination. Mol Cell. 21(5): 641-651. 
PubMed Reference

Carroll, K.L., Pradhan, D.A., Granek, J.A., Clarke, N.D., and J. L. Corden (2004) Identification of Cis-Elements Directing Termination of Yeast Non-polyadenylated snoRNA Transcripts. Mol Cell Biol. 24(14); 6241-6252. 
PubMed Reference

Doyle, O., Corden, J.L., Murphy, C., and Gall, J.G. (2002) The distribution of RNA polymerase II largest subunit in the Xenopus germinal vesicle. J. Struct. Biol. 140: 154. 
PubMed Reference

Steinmetz, E.J., Conrad, N.K., Brow, D.A. and Corden, J.L. (2001) RNA-binding protein Nrd1 directs poly(A)-independent 3'-end formation of RNA Polymerase II transcripts. Nature. 413: 6853. 
PubMed Abstract

Conrad, N. K., Wilson, S.M., Steinmetz, E.J., Patturajan, M., Brow, D.A., Swanson, M.S., and Corden, J.L. (2000) A Nrd1p-Nab3p complex associated with RNA polymerase II. Genetics. 154: 557-571. 
PubMed Abstract

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