ReguloBac-3UTR Project ERC Consolidator Grant

Eukaryotic untranslated regions located at the 3′ end (3’-UTRs) of messenger RNAs (mRNAs) are key post-transcriptional regulatory elements controlling almost every single biological process. In contrast, in bacteria, most studies regarding post-transcriptional regulation have been mainly focused on specific non-coding RNAs (both asRNAs and sRNAs) and 5’-UTRs, which often carry riboswitches or thermosensors. Remarkably, bacterial 3’-UTRs have been largely disregarded and have not been considered as potential regulatory elements.

Although some previous studies showed the potential of bacterial 3’UTRs to control important biological processes such as multicellular behaviour and virulence, many questions still remain to be answered.

– Are 3’-UTRs roles conserved in bacterial species?
– Do 3’-UTRs contain specific regulatory sequences and/or secondary RNA structures?
– Are transcriptional terminator sequences relevant for certain 3’-UTRs?
– Are 3’-UTRs specifically recognized by ribonucleases and/or RNA-binding proteins?
– Might 3’-UTRs be responsible for bacterial speciation?
– Is bacterial 3’-UTR-mediated regulation as general as in eukaryotes?
– Might bacterial 3’-UTRs be the ancestors of eukaryotic 3’-UTR evolution?

In order to achieve these questions, the ReguloBac-3UTR focused on high-throughput analyses to identify genome-wide functional regulatory 3’-UTRs. Also the pool of RNA-binding proteins associated to 3’-UTRs will be investigated.

Finally, relevant examples of 3’-UTRs belonging to physiologically important genes will be selected to deeply study the regulatory mechanisms at the molecular and single-cell levels. We expect that this project will largely change the view of post- transcriptional regulation in bacteria. The understanding of genomic organizations that lead to post- transcriptional regulatory mechanisms that have not been considered up to now will help to improve microbiology, synthetic biology and biotechnology fields. In addition, the finding of new regulatory layers will imply new potential targets for the development of novel antimicrobials that might contribute to deal with the challenging issue of multi-drug antibiotic resistance, a worldwide problem.