Gene expression in normal and pathological conditions is mediated by RNA polymerase enzymes, a family of complex, multisubunit molecular machines that is highly conserved in evolution. RNA polymerase function is controlled not only at the level of access to genes (transcription initiation), but also during enzyme progression as RNAP carries out its sequential readout of the gene message. An important example of such control occurs in HIV virus and is mediated by its major regulator, the TAT gene. The central models for understanding enzymatic mechanisms involved in transcriptional regulation are the antitermination proteins of the E. coli bacteriophage lambda, the products of its genes Q and N. This project studies the mechanism of action of the gene Q protein, which modifies RNA polymerase near its initiation site, but then becomes a subunit of the enzyme, allowing it to elongate more efficiently and to progress through transcription termination signals. We will discover important elements of both the Q polypeptide and the subunits of RNA polymerase that are required for their physical and functional interaction, particularly the sigma initiation factor which mediates the initial engagement of Q protein with RNA polymerase, and we will study the altered enzymatic properties of Q-modified RNA polymerase. We will investigate the mechanism of transcription termination and the manner in which regulatory proteins interfere with this process.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Method to Extend Research in Time (MERIT) Award (R37)
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Special Emphasis Panel (NSS)
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Tompkins, Laurie
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Cornell University
Schools of Earth Sciences/Natur
United States
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Strobel, Eric J; Roberts, Jeffrey W (2015) Two transcription pause elements underlie a ?70-dependent pause cycle. Proc Natl Acad Sci U S A 112:E4374-80
Strobel, Eric J; Roberts, Jeffrey W (2014) Regulation of promoter-proximal transcription elongation: enhanced DNA scrunching drives ?Q antiterminator-dependent escape from a ?70-dependent pause. Nucleic Acids Res 42:5097-108
Liu, Xiaoqiu; Jiang, Huifeng; Gu, Zhenglong et al. (2013) High-resolution view of bacteriophage lambda gene expression by ribosome profiling. Proc Natl Acad Sci U S A 110:11928-33
Perdue, Sarah A; Roberts, Jeffrey W (2010) A backtrack-inducing sequence is an essential component of Escherichia coli ?(70)-dependent promoter-proximal pausing. Mol Microbiol 78:636-50
Shankar, Smita; Hatoum, Asma; Roberts, Jeffrey W (2007) A transcription antiterminator constructs a NusA-dependent shield to the emerging transcript. Mol Cell 27:914-27
Park, Joo-Seop; Roberts, Jeffrey W (2006) Role of DNA bubble rewinding in enzymatic transcription termination. Proc Natl Acad Sci U S A 103:4870-5
Nickels, Bryce E; Roberts, Christine W; Roberts, Jeffrey W et al. (2006) RNA-mediated destabilization of the sigma(70) region 4/beta flap interaction facilitates engagement of RNA polymerase by the Q antiterminator. Mol Cell 24:457-68
Holmes, Shannon F; Santangelo, Thomas J; Cunningham, Candice K et al. (2006) Kinetic investigation of Escherichia coli RNA polymerase mutants that influence nucleotide discrimination and transcription fidelity. J Biol Chem 281:18677-83
Wickstrum, Jason R; Santangelo, Thomas J; Egan, Susan M (2005) Cyclic AMP receptor protein and RhaR synergistically activate transcription from the L-rhamnose-responsive rhaSR promoter in Escherichia coli. J Bacteriol 187:6708-18
Guo, Jingshu; Roberts, Jeffrey W (2004) DNA binding regions of Q proteins of phages lambda and phi80. J Bacteriol 186:3599-608

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