Stem-Loop Structures within mRNA Coding Sequences Activate Translation Initiation and Mediate Control by Small Regulatory RNAs

Mol Cell. 2017 Oct 5;68(1):158-170.e3. doi: 10.1016/j.molcel.2017.08.015. Epub 2017 Sep 14.

Abstract

Initiation is the rate-limiting step of translation, and in bacteria, mRNA secondary structure has been extensively reported as limiting the efficiency of translation by occluding the ribosome-binding site. In striking contrast with this inhibitory effect, we report here that stem-loop structures located within coding sequences instead activate translation initiation of the Escherichia coli fepA and bamA mRNAs involved in iron acquisition and outer membrane proteins assembly, respectively. Both structures promote ribosome binding in vitro, independently of their nucleotide sequence. Moreover, two small regulatory RNAs, OmrA and OmrB, base pair to and most likely disrupt the fepA stem-loop structure, thereby repressing FepA synthesis. By expanding our understanding of how mRNA cis-acting elements regulate translation, these data challenge the widespread view of mRNA secondary structures as translation inhibitors and show that translation-activating elements embedded in coding sequences can be targeted by small RNAs to inhibit gene expression.

Keywords: BAM complex; Hfq; enterobactin; non-coding RNA; regulatory RNA; regulatory mechanism; siderophore; starting block; toeprint; translation-activating structure.

MeSH terms

  • Bacterial Outer Membrane Proteins / genetics*
  • Bacterial Outer Membrane Proteins / metabolism
  • Base Pairing
  • Base Sequence
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Gene Expression Regulation, Bacterial*
  • Inverted Repeat Sequences
  • Iron / metabolism
  • Nucleic Acid Conformation
  • Open Reading Frames
  • Peptide Chain Initiation, Translational
  • RNA, Bacterial / genetics*
  • RNA, Bacterial / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA, Small Untranslated / genetics*
  • RNA, Small Untranslated / metabolism
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Ribosomes / genetics
  • Ribosomes / metabolism

Substances

  • Bacterial Outer Membrane Proteins
  • BamA protein, E coli
  • Carrier Proteins
  • Escherichia coli Proteins
  • RNA, Bacterial
  • RNA, Messenger
  • RNA, Small Untranslated
  • Receptors, Cell Surface
  • enterobactin receptor
  • Iron