Feedback regulation of small RNA processing by the cleavage product

RNA Biol. 2019 Aug;16(8):1055-1065. doi: 10.1080/15476286.2019.1612693. Epub 2019 May 22.


Many bacterial small RNAs (sRNAs) are processed resulting in variants with roles potentially distinct from the primary sRNAs. In Enterobacteriaceae sRNA GlmZ activates expression of glmS by base-pairing when the levels of glucosamine-6-phosphate (GlcN6P) are low. GlmS synthesizes GlcN6P, which is required for cell envelope biosynthesis. When dispensable, GlmZ is cleaved by RNase E in the base-pairing sequence. Processing requires protein RapZ, which binds GlmZ and recruits RNase E by interaction. Cleavage is counteracted by the homologous sRNA GlmY, which accumulates upon GlcN6P scarcity and sequesters RapZ. Here, we report a novel role for a processed sRNA. We observed that processing of GlmZ is never complete in vivo. Even upon RapZ overproduction, a fraction of GlmZ remains full-length, while the 5' cleavage product (GlmZ*) accumulates. GlmZ* retains all elements required for RapZ binding. Accordingly, GlmZ* can displace full-length GlmZ from RapZ and counteract processing in vitro. To mimic GlmZ* in vivo, sRNA chimeras were employed consisting of foreign 3' ends including a terminator fused to the 3' end of GlmZ*. In vitro, these chimeras perform indistinguishable from GlmZ*. Expression of the chimeras in vivo inhibited processing of endogenous GlmZ, causing moderate upregulation of GlmS synthesis. Hence, accumulation of GlmZ* prevents complete GlmZ turnover. This mechanism may serve to adjust a robust glmS basal expression level that is buffered against fluctuations in RapZ availability.

Keywords: RNA processing; RNase E; Small RNA GlmZ; adaptor protein RapZ; feedback regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics*
  • Endoribonucleases / genetics*
  • Escherichia coli / genetics
  • Escherichia coli Proteins / genetics*
  • Feedback, Physiological
  • Gene Expression Regulation, Bacterial / genetics
  • Glucosamine / analogs & derivatives
  • Glucosamine / genetics
  • Glucose-6-Phosphate / analogs & derivatives
  • Glucose-6-Phosphate / genetics
  • RNA, Bacterial / genetics
  • RNA, Messenger / genetics
  • RNA, Small Untranslated / genetics
  • RNA-Binding Proteins / genetics*
  • Transcription Factors / genetics*


  • Bacterial Proteins
  • Escherichia coli Proteins
  • PsrA protein, E coli
  • RNA, Bacterial
  • RNA, Messenger
  • RNA, Small Untranslated
  • RNA-Binding Proteins
  • Transcription Factors
  • YhbJ protein, E coli
  • component S, glutamate mutase protein, Bacteria
  • glucosamine 6-phosphate
  • Glucose-6-Phosphate
  • Endoribonucleases
  • ribonuclease E
  • Glucosamine

Grant support

This work was supported by the Austrian Science Fund [Doktoratskolleg RNA Biology W1207-B09]; Austrian Science Fund [RNA-REG F43; F4317].