A role for REP sequences in regulating translation

Mol Cell. 2015 May 7;58(3):431-9. doi: 10.1016/j.molcel.2015.03.019. Epub 2015 Apr 16.

Abstract

Repetitive extragenic palindromic (REP) sequences are highly structured elements found downstream of ∼500 genes in Escherichia coli that result in extensive stem-loop structures in their mRNAs. However, their physiological role has remained elusive. Here, we show that REP sequences can downregulate translation, but only if they are within 15 nt of a termination codon; a spacing of 16 nt has no effect, suggesting that the REP element acts to stall ribosome movement. Ribosome stalling leads to cleavage of the mRNA and induction of the trans-translation process. Using nrdAB as a model, we find that its regulation can be partially reversed by overexpression of RNA helicases and can be fully overcome upon UV stress, emphasizing the importance of this regulatory process. Since 50% of REP-associated genes have these elements within the critical 15 nt, these findings identify a regulatory mechanism with the potential to affect translation from a large number of genes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics*
  • Models, Genetic
  • Protein Biosynthesis*
  • RNA Stability
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Ribonucleoside Diphosphate Reductase / genetics
  • Ribonucleotide Reductases / genetics

Substances

  • Escherichia coli Proteins
  • RNA, Messenger
  • NrdB protein, E coli
  • Ribonucleotide Reductases
  • NrdA protein, E coli
  • Ribonucleoside Diphosphate Reductase