RelA binding of mRNAs modulates translation or sRNA-mRNA basepairing depending on the position of the GGAG site

Pallabi Basu, Shoshy Altuvia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Previously, we reported that RelA protein facilitates Hfq-mediated mRNA-sRNA regulation by binding sRNAs carrying a Shine-Dalgarno-like GGAG sequence. In turn, sRNA-Hfq monomers are stabilized, enabling the attachment of more Hfq subunits to form a functional hexamer. Here, using CLIP-seq, we present a global analysis of RelA-bound RNAs showing that RelA interacts with sRNAs as well as with mRNAs carrying a GGAG motif. RelA binding of mRNAs carrying GGAG at position −7 relative to the initiation codon (AUG) inhibits translation by interfering with the binding of 30S ribosomes. The extent of inhibition depends on the distance of GGAG relative to the AUG, as shortening the spacing between GGAG and AUG abrogates RelA-mediated inhibition. Interestingly, RelA binding of target mRNAs carrying GGAG in the coding sequence or close to AUG facilitates target gene regulation by sRNA partners that lack GGAG. However, translation inhibition caused by RelA binding of mRNAs carrying GGAG at position −7 relative to the AUG renders sRNA-mRNA basepairing regulation ineffective. Our study indicates that by binding RNAs carrying GGAG the ribosome-associated RelA protein inhibits translation of specific newly synthesized incoming mRNAs or enables basepairing regulation by their respective sRNA partners, thereby introducing a new regulatory concept for the bacterial response.

Original languageAmerican English
Pages (from-to)143-159
Number of pages17
JournalMolecular Microbiology
Volume117
Issue number1
DOIs
StatePublished - Jan 2022

Bibliographical note

Publisher Copyright:
© 2021 John Wiley & Sons Ltd.

Keywords

  • Base Pairing
  • Escherichia coli Proteins/genetics
  • Escherichia coli/genetics
  • GTP Pyrophosphokinase/genetics
  • Nucleotide Motifs
  • Protein Biosynthesis
  • RNA, Bacterial/genetics
  • RNA, Messenger/genetics
  • RNA, Small Untranslated/genetics
  • RNA-Binding Proteins/genetics
  • Ribosomes/metabolism

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