Alkylative damage of mRNA leads to ribosome stalling and rescue by <i>trans</i> translation in bacteria.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32940602.
- Also identified by DOI 10.7554/eLife.61984 and PMC identifier 7521929.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Similar to DNA replication, translation of the genetic code by the ribosome is hypothesized to be exceptionally sensitive to small chemical changes to its template mRNA. Here we show that the addition of common alkylating agents to growing cultures of <i>Escherichia coli</i> leads to the accumulation of several adducts within RNA, including N(1)-methyladenosine (m<sup>1</sup>A). As expected, the introduction of m<sup>1</sup>A to model mRNAs was found to reduce the rate of peptide bond formation by three orders of magnitude in a well-defined in vitro system. These observations suggest that alkylative stress is likely to stall translation in vivo and necessitates the activation of ribosome-rescue pathways. Indeed, the addition of alkylation agents was found to robustly activate the transfer-messenger RNA system, even when transcription was inhibited. Our findings suggest that bacteria carefully monitor the chemical integrity of their mRNA and they evolved rescue pathways to cope with its effect on translation.
Medical subject headings
- Alkylating Agents
- Protein Biosynthesis
- RNA, Bacterial
- RNA, Messenger
- Ribosomes