Exploring biogenesis and functions of 3'UTR-derived small regulatory RNAs

• Applicant: Professor Dr. Jörg Vogel
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 278016524

Most investigations of small regulatory RNAs (sRNAs) have focused on transcripts from noncoding genes in the intergenic regions of bacterial chromosomes. However, there is growing evidence to suggest that the 3-prime regions of mRNA genes constitute an additional large reservoir from which new sRNAs evolve. To date, very few such 3-prime UTR-derived sRNAs have been investigated with respect to function, and both the biogenesis principles and regulation of the cellular targets of this emerging class of bacterial riboregulators remain to be elucidated. In this project we will focus on 3-prime UTR-derived sRNAs that are generated through mRNA processing and ask if such sRNAs function in the same pathway as the proteins from their parental mRNAs. To this end, we have selected two promising candidates, CpxQ and RybD, with predicted roles in envelope stress control and metabolic regulation, respectively. Both these 3-prime UTR-derived sRNAs are well-conserved, associate with Hfq protein, and show expression indicative of a condition-dependent function; one is made from a monocistronic mRNA of an important chaperone in the bacterial Cpx stress pathway, the other from the long operon mRNA of important metabolic enzymes. Each of these two sRNAs is attractive for additional reasons: CpxQ may be a missing link in the conserved CpxR-mediated stress response that is emerging as a new drug target; RybD may be the shortest functional Hfq-associated sRNA known to date and lends itself as a model for high-resolution structural analysis. More generally, understanding the cellular roles of these 3-prime UTR-derived sRNAs will provide insight into the fundamental question why in some situations cells favour regulatory RNA molecules over regulatory proteins.

• DFG Programme: Research Grants