4.8 Article

Rewiring of growth-dependent transcription regulation by a point mutation in region 1.1 of the housekeeping σ factor

Journal

NUCLEIC ACIDS RESEARCH
Volume 48, Issue 19, Pages 10802-10819

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/nar/gkaa798

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Funding

  1. Russian Science Foundation [17-14-01393, 19-14-00043]
  2. Russian Foundation for BasicResearch [18-34-20095]
  3. Russian Science Foundation
  4. Russian Science Foundation [19-14-00043, 20-14-18016] Funding Source: Russian Science Foundation

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In bacteria, rapid adaptation to changing environmental conditions depends on the interplay between housekeeping and alternative sigma factors, responsible for transcription of specific regulons by RNA polymerase (RNAP). In comparison with alternative sigma factors, primary sigma s contain poorly conserved region 1.1, whose functions in transcription are only partially understood. We found that a single mutation in region 1.1 in Escherichia coli sigma(70) rewires transcription regulation during cell growth resulting in profound phenotypic changes. Despite its destabilizing effect on promoter complexes, this mutation increases the activity of rRNA promoters and also decreases RNAP sensitivity to the major regulator of stringent response DksA. Using total RNA sequencing combined with single-cell analysis of gene expression we showed that changes in region 1.1 disrupt the balance between the greed and fear strategies thus making the cells more susceptible to environmental threats and antibiotics. Our results reveal an unexpected role of sigma region 1.1 in growth-dependent transcription regulation and suggest that changes in this region may facilitate rapid switching of RNAP properties in evolving bacterial populations.

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