Alkylative damage of mRNA leads to ribosome stalling and rescue by trans translation in bacteria.

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 Escherichia coli leads to the accumulation of several adducts within RNA, including N(1)-methyladenosine (m¹A). As expected, the introduction of m¹A 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-

SUBMITTER: Thomas EN 

PROVIDER: S-EPMC7521929 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature