REDBAC (101116636)

  https://cordis.europa.eu/project/id/101116636

  Horizon Europe (2021-2027)

  Occurrence, Regulation, and Function of Bacterial mRNA Editing Under Diverse Environments

  ERC STARTING GRANTS (ERC-2023-STG)

  proteomics  ·  bacteriology  ·  physiology  ·  RNA  ·  enzymes

  2023-09-01 Start Date (YY-MM-DD)

  2028-08-31 End Date (YY-MM-DD)

  € 1,749,998

  Description

"Bacteria are haploid, having a single copy of each gene. We suggest a paradigm shift in bacterial genetics: bacteria can have two RNA versions of the same gene, encoding protein isoforms at the single-bacterium and population level. These protein isoforms can have altered activity, which could be advantageous under different conditions. Adenosine-to-inosine (A-to-I) mRNA editing can affect the sequence and the function of translated proteins because the ribosome identifies inosine as guanosine. We discovered that A-to-I mRNA editing occurs in bacteria (Escherichia coli), identified the mediating enzyme, and showed that it could affect protein function. Moreover, we discovered that environmental cues experienced during growth in culture affect bacterial mRNA editing. However, the prevalence and regulation of A-to-I mRNA editing across bacteria and the importance of editing for protein function and bacterial physiology in different environments are still unknown. Here, we will test the hypothesis that mRNA editing is widespread in bacteria, producing two RNA ""alleles"" (pseudo-heterozygosity). Subsequently, these RNA ""alleles"" may co-exist in the same bacterial cell or population of cells. Thus, mRNA editing may enable the translation of protein isoforms, making bacteria better adapted to changing environments. We suggest (1) identifying mRNA editing events across environmental conditions in hundreds of species, (2) uncovering the regulatory genetic factors governing bacterial mRNA editing occurrence, and (3) determining the effect of mRNA editing on the proteome and its functional role in bacteria. Our work could shed light on a new mechanism bacteria employ to grow and survive in different environments. Furthermore, bacterial mRNA editing—invisible to DNA sequencing—may account for unsolved problems or phenomena that current genetic and proteomic data cannot explain, affecting bacterial biology and human health."

  Complicit Organisations

1 Israeli organisation participates in REDBAC.