Determinants of target prioritization and regulatory hierarchy for the bacterial small RNA SgrS

Maksym Bobrovskyy, Muhammad S. Azam, Jane K. Frandsen, Jichuan Zhang, Anustup Poddar, Xiangqian Ma, Tina M. Henkin, Taekjip Ha, Carin K. Vanderpool

Research output: Contribution to journalArticle

Abstract

Small RNA (sRNA) regulators promote efficient responses to stress, but the mechanisms for prioritizing target mRNA regulation remain poorly understood. This study examines mechanisms underlying hierarchical regulation by the sRNA SgrS, found in enteric bacteria and produced under conditions of metabolic stress. SgrS posttranscriptionally coordinates a nine-gene regulon to restore growth and homeostasis. An in vivo reporter system quantified SgrS-dependent regulation of target genes and established that SgrS exhibits a clear target preference. Regulation of some targets is efficient even at low SgrS levels, whereas higher SgrS concentrations are required to regulate other targets. In vivo and in vitro analyses revealed that RNA structure and the number and position of base pairing sites relative to the start of translation impact the efficiency of regulation of SgrS targets. The RNA chaperone Hfq uses distinct modes of binding to different SgrS mRNA targets, which differentially influences positive and negative regulation. The RNA degradosome plays a larger role in regulation of some SgrS targets compared to others. Collectively, our results suggest that sRNA selection of target mRNAs and regulatory hierarchy are influenced by several molecular features and that the combination of these features precisely tunes the efficiency of regulation of multi-target sRNA regulons.

Original languageEnglish (US)
JournalMolecular Microbiology
DOIs
StateAccepted/In press - Jan 1 2019

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Bacterial RNA
RNA
Regulon
Messenger RNA
Physiological Stress
Enterobacteriaceae
Base Pairing
Genes
Homeostasis
Growth

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Bobrovskyy, M., Azam, M. S., Frandsen, J. K., Zhang, J., Poddar, A., Ma, X., ... Vanderpool, C. K. (Accepted/In press). Determinants of target prioritization and regulatory hierarchy for the bacterial small RNA SgrS. Molecular Microbiology. https://doi.org/10.1111/mmi.14355

Determinants of target prioritization and regulatory hierarchy for the bacterial small RNA SgrS. / Bobrovskyy, Maksym; Azam, Muhammad S.; Frandsen, Jane K.; Zhang, Jichuan; Poddar, Anustup; Ma, Xiangqian; Henkin, Tina M.; Ha, Taekjip; Vanderpool, Carin K.

In: Molecular Microbiology, 01.01.2019.

Research output: Contribution to journalArticle

Bobrovskyy, M, Azam, MS, Frandsen, JK, Zhang, J, Poddar, A, Ma, X, Henkin, TM, Ha, T & Vanderpool, CK 2019, 'Determinants of target prioritization and regulatory hierarchy for the bacterial small RNA SgrS', Molecular Microbiology. https://doi.org/10.1111/mmi.14355
Bobrovskyy, Maksym ; Azam, Muhammad S. ; Frandsen, Jane K. ; Zhang, Jichuan ; Poddar, Anustup ; Ma, Xiangqian ; Henkin, Tina M. ; Ha, Taekjip ; Vanderpool, Carin K. / Determinants of target prioritization and regulatory hierarchy for the bacterial small RNA SgrS. In: Molecular Microbiology. 2019.
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