The goal is to understand the function of a transcription antiterminator, a regulatory protein of the universal transcription enzyme RNA polymerase. The bacteriophage lambda gene Q protein promotes phage late gene expression by interacting with RNA polymerase at a particular, genome-specific site, modifying the enzyme so that it reads through transcription terminators that otherwise prevent phage late gene expression. Antitermination is less well understood than regulation of RNA chain initiation, but it is common in bacteria, and is appearing frequently in higher cells: antitermination has been implicated in control of the cellular oncogene myc, in growth of the tumor viruses SV40 and adenovirus, and in control of HIV expression by the tat gene product. The lambda Q protein is a well characterized, purified regulator that works in a defined in vitro transcription system, 30 that its mechanism can be studied in biochemical detail. We intend to determine how Q protein interacts with DNA or RNA to carry out its genome-specific recognition and how it modifies the properties of RNA polymerase. We will pursue indications that Q protein modifies the fundamental kinetic properties of RNA polymerase to promote elongation through barriers like terminators. We will develop a genetic analysis of Q protein and RNA polymerase that should help characterize the physical and functional interaction of Q protein with the enzyme, and will complement our continuing biochemical characterization of antitermination. At the same time these studies will increase understanding of transcription termination, a process universally involved in control of RNA synthesis and gene expression.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Microbial Physiology and Genetics Subcommittee 2 (MBC)
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Cornell University
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Bird, Jeremy G; Strobel, Eric J; Roberts, Jeffrey W (2016) A universal transcription pause sequence is an element of initiation factor ?70-dependent pausing. Nucleic Acids Res 44:6732-40
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
Hatoum, Asma; Roberts, Jeffrey (2008) Prevalence of RNA polymerase stalling at Escherichia coli promoters after open complex formation. Mol Microbiol 68:17-28
Roberts, Jeffrey W; Shankar, Smita; Filter, Joshua J (2008) RNA polymerase elongation factors. Annu Rev Microbiol 62:211-33
Davydova, Elena K; Santangelo, Thomas J; Rothman-Denes, Lucia B (2007) Bacteriophage N4 virion RNA polymerase interaction with its promoter DNA hairpin. Proc Natl Acad Sci U S A 104:7033-8
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
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

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