A 3' UTR-Derived Small RNA Provides the Regulatory Noncoding Arm of the Inner Membrane Stress Response

Mol Cell. 2016 Feb 4;61(3):352-363. doi: 10.1016/j.molcel.2015.12.023. Epub 2016 Jan 21.


Small RNAs (sRNAs) from conserved noncoding genes are crucial regulators in bacterial signaling pathways but have remained elusive in the Cpx response to inner membrane stress. Here we report that an alternative biogenesis pathway releasing the conserved mRNA 3' UTR of stress chaperone CpxP as an ∼60-nt sRNA provides the noncoding arm of the Cpx response. This so-called CpxQ sRNA, generated by general mRNA decay through RNase E, acts as an Hfq-dependent repressor of multiple mRNAs encoding extracytoplasmic proteins. Both CpxQ and the Cpx pathway are required for cell survival under conditions of dissipation of membrane potential. Our discovery of CpxQ illustrates how the conversion of a transcribed 3' UTR into an sRNA doubles the output of a single mRNA to produce two factors with spatially segregated functions during inner membrane stress: a chaperone that targets problematic proteins in the periplasm and a regulatory RNA that dampens their synthesis in the cytosol.

Keywords: 3′ UTR; Cpx pathway; CpxP; CpxQ; Hfq; NhaB; RNase E; envelope stress; membrane potential; noncoding RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions*
  • Bacteria / genetics
  • Bacteria / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Base Sequence
  • Cell Membrane / metabolism*
  • Conserved Sequence
  • Endoribonucleases / metabolism
  • Gene Expression Regulation, Bacterial
  • Membrane Potentials
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microbial Viability
  • Molecular Sequence Data
  • RNA Processing, Post-Transcriptional*
  • RNA, Bacterial / genetics
  • RNA, Bacterial / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA, Small Untranslated / genetics
  • RNA, Small Untranslated / metabolism*
  • Signal Transduction
  • Stress, Psychological*
  • Time Factors


  • 3' Untranslated Regions
  • Bacterial Proteins
  • CpxP protein, bacteria
  • Membrane Proteins
  • RNA, Bacterial
  • RNA, Messenger
  • RNA, Small Untranslated
  • Endoribonucleases
  • ribonuclease E