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

Science  30 May 2014:
Vol. 344, Issue 6187, pp. 1042-1047
DOI: 10.1126/science.1251871

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Transcription takes a pause to consider

A short sequence in DNA causes RNA polymerase (RNAP) to pause at thousands of previously undocumented locations in the genome. Larson et al. mapped these pause sites at single-nucleotide resolution in vivo in actively growing bacteria. Transcriptional pausing can be critical for the regulation of gene expression, by allowing RNA folding events and in the recruitment of other transcription factors.

Science, this issue p. 1042

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.

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