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Science. 2014 May 30;344(6187):1042-7. doi: 10.1126/science.1251871. Epub 2014 May 1.

A pause sequence enriched at translation start sites drives transcription dynamics in vivo.

Author information

1
Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, California Institute for Quantitative Biosciences, Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
2
Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
3
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
4
Department of Biological Sciences, Stanford University, Stanford, CA 94025, USA. Department of Applied Physics; Stanford University, Stanford, CA 94025, USA.
5
Department of Genetics, Stanford University, Stanford, CA 94025, USA. wjg@stanford.edu landick@biochem.wisc.edu weissman@cmp.ucsf.edu.
6
Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA. Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA. wjg@stanford.edu landick@biochem.wisc.edu weissman@cmp.ucsf.edu.
7
Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, California Institute for Quantitative Biosciences, Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. wjg@stanford.edu landick@biochem.wisc.edu weissman@cmp.ucsf.edu.

Abstract

Transcription by RNA polymerase (RNAP) is interrupted by pauses that play diverse regulatory roles. Although individual pauses have been studied in vitro, the determinants of pauses in vivo and their distribution throughout the bacterial genome remain unknown. Using nascent transcript sequencing, we identified a 16-nucleotide consensus pause sequence in Escherichia coli that accounts for known regulatory pause sites as well as ~20,000 new in vivo pause sites. In vitro single-molecule and ensemble analyses demonstrate that these pauses result from RNAP-nucleic acid interactions that inhibit next-nucleotide addition. The consensus sequence also leads to pausing by RNAPs from diverse lineages and is enriched at translation start sites in both E. coli and Bacillus subtilis. Our results thus reveal a conserved mechanism unifying known and newly identified pause events.

PMID:
24789973
PMCID:
PMC4108260
DOI:
10.1126/science.1251871
[Indexed for MEDLINE]
Free PMC Article

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