Living organisms regulate their gene expression to adapt to changing environmental conditions through a variety of molecular mechanisms. Regulation at the level of RNA, also known as post-transcriptional control, is particularly important as it enables fast, nuanced and complex cellular responses. It relies on noncoding RNAs and RNA-binding proteins. Some of these proteins are pleiotropic: they regulate dozens and even hundreds of cellular transcripts. Such global RNA-binding factors (RNA-binding hubs) play essential roles in organising and empowering post-transcriptional networks in apparently all species.
The functional significance of several RNA-binding hubs has been extensively studied with biochemical and genetic approaches, which revealed how they work, what they regulate, and why it is important for the cell. However, we still lack understanding of why diverse organisms throughout evolution employ such proteins to coordinate their gene expression. Are RNA-binding hubs so essential in the long run? Can a bacterium learn to thrive without them? Would their loss provoke the emergence of new regulatory or biogenesis modes?
This project aims to experimentally test the evolutionary importance of three major bacterial RNA-binding hubs, the global RNA chaperones Hfq and ProQ and the ultraconserved ribosome assembly factor YbeY, which, via different mechanisms, control a large part of the E. coli genome. We employ the ‘modify-and-evolve’ approach and analyse the long-term consequences of losing each of these key proteins on the well-being of bacteria. In an long-run adaptive evolution experiment, we follow how an organism with essentially destroyed post-transcriptional networks finds evolutionary trajectories to restore its fitness without recurring to the missing regulator. Such data are essential for the understanding of key speciation events, which often involve dramatic rewiring of regulatory networks with little change in the gene content of an organism.
