The University of Massachusetts Amherst

Craig Martin

Professor

My group has a longstanding interest in structure and function in enzyme-nucleic acid interactions, with a particular focus on the enzymology of transcription. To understand fundamental mechanisms in the complex process of transcription, we have mostly focused our work on the single subunit model RNA polymerase from bacteriophage T7.

Current Research

In addition to serving as a model system, T7 RNA polymerase is widely used as a tool to synthesize RNA in vitro. This is critical to the vast “RNA world” of academic researchers, and particularly critical in the growing field of RNA therapeutics. Full development of the latter is hampered by an unintended immune response evoked by, we believe, RNA byproducts in the RNA of interest.

Using new applications of RNA-Seq (massively parallel sequencing of in vitro transcription products), we have recently demonstrated that “high yield” transcription conditions drive rebinding of nascent RNA to the polymerase, in a mode that allows self-templated extension of the RNA to form longer, partially double-stranded products. The self-templated extension is independent of DNA and is highly sequence dependent.

We are now developing mechanism-based approaches towards the synthesis of RNA with much great purity (and yield!). Adding the tool of RNA-Seq, which provides far more information than traditional gel electrophoresis, we are expanding our understanding of and characterizing fully a variety of aspects of the transcription process. We anticipate huge impacts across the rapidly expanding RNA universe!

Learn more at https://martinlab.chem.umass.edu

Academic Background

  • BA University of California/San Diego
  • PhD California Institute of Technology 1984
  • Postdoctoral Training: NIH Postdoctoral Fellowship, Yale University 1985-1988,
“3′ end additions by T7 RNA polymerase are RNA self-templated, distributive and diverse in character—RNA-Seq analyses ,” Yasaman Gholamalipour, Aruni Karunanayake Mudiyanselage, & Craig T. Martin, Nucleic Acids Res. 46, 9253–63, 2019. Selected by the editors as a “Breakthrough Article.” https://doi.org/10.1093/nar/gky796
“Efficient inhibition of RNA self-primed extension by addition of competing 3’-capture DNA – improved RNA synthesis by T7 RNA polymerase,” Yasaman Gholamalipour, William C. Johnson, & Craig T. Martin, Nucleic Acids Res. pending, 2019.
"Insights into the Mechanism of Initial Transcription in E coli RNA Polymerase. Energetic Mechanisms Leading to Initial Complex Instability and Abortive Cycling," Satamita, Samanta & Craig T. Martin, J. Biol. Chem. 288, 31993-32003, 2013.
"New Insights into the Mechanism of Initial Transcription: the T7 RNA Polymerase Mutant P266L Transitions to Elongation at Longer RNA Lengths than Wild Type," Luis Ramírez-Tapia & Craig T. Martin, J. Biol. Chem. 287, 37352-37361, 2012.
"Direct Tests of the Energetic Basis of Abortive Cycling in Transcription," Ankit V. Vahia & Craig T. Martin, Biochemistry 50, 7015-7022, 2011.
"Transcription Elongation Complex Stability: The Topological Lock," Xiaoqing Liu & Craig T. Martin, J. Biol. Chem. 284, 36262-36270, 2009.
"Dissociation of halted T7 RNA polymerase elongation complexes proceeds via a forward translocation mechanism," Yi Zhou, Deanna M. Navaroli, Metewo Selase Enuameh, & Craig T. Martin, Proc. Natl. Acad. Sci., U.S.A. 104, 10352-10357, 2007.
 
Contact Info

Department of Chemistry
862 Lederle Graduate Research Tower
710 North Pleasant Street
Amherst, MA 01003

(413) 545-3299
cmartin@chem.umass.edu

people.chem.umass.edu/cmartin/