Reports

Termination Factor Rho and Its Cofactors NusA and NusG Silence Foreign DNA in E. coli

Christopher J. Cardinale,^1* Robert S. Washburn,^2* Vasisht R. Tadigotla,³ Lewis M. Brown,⁴ Max E. Gottesman,^2,5 Evgeny Nudler¹

Transcription of the bacterial genome by the RNA polymerase must terminate at specific points. Transcription can be terminated by Rho factor, an essential protein in enterobacteria. We used the antibiotic bicyclomycin, which inhibits Rho, to assess its role on a genome-wide scale. Rho is revealed as a global regulator of gene expression that matches Escherichia coli transcription to translational needs. We also found that genes in E. coli that are most repressed by Rho are prophages and other horizontally acquired portions of the genome. Elimination of these foreign DNA elements increases resistance to bicyclomycin. Although rho remains essential, such reduced-genome bacteria no longer require Rho cofactors NusA and NusG. Deletion of the cryptic rac prophage in wild-type E. coli increases bicyclomycin resistance and permits deletion of nusG. Thus, Rho termination, supported by NusA and NusG, is required to suppress the toxic activity of foreign genes.

¹ Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
² Department of Microbiology, Columbia University Medical Center, New York, NY 10032, USA.
³ BioMaPS Institute for Quantitative Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
⁴ Comparative Proteomics Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
⁵ Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032, USA.

^* These authors contributed equally to this work.

Present address: Department of Physics, Boston University, Boston, MA 02215, USA.

To whom correspondence should be addressed. E-mail: evgeny.nudler{at}med.nyu.edu (E.N.); meg8{at}columbia.edu (M.E.G.)

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PNAS 106, 15406-15411
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PNAS 105, 18159-18164
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A. V. Yakhnin, H. Yakhnin, and P. Babitzke (2008)
PNAS 105, 16131-16136
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