Physiologie et biochimie des petits ARN régulateurs

Chercheurs-boursiers - Senior | Concours 2012-2013


Éric Massé

Université de Sherbrooke

 

Domaine : Maladies infectieuses et immunitaires

Iron (Fe) is the most important metal ion for the majority of organisms. This metal is used in iron-sulfur cluster proteins that catalyze critical enzymatic reactions in the tricarboxylic acid (TCA) cycle, respiration, gene expression, and DNA biosynthesis and repair. However, because iron is extremely scarce under physiological conditions, some pathogenic bacteria have developed aggressive strategies in order to scavenge iron from different sources, including their eukaryotic hosts. Despite its important role in microbial infection, little is known about the regulation of intracellular iron and its influence on gene expression. My group has elucidated a new mechanism through which RyhB, a small regulatory RNA (sRNA), regulates the expression of iron-using proteins. This discovery has opened a novel perspective on the fundamental problem of iron acquisition and distribution in cells. 
Although sRNAs are numerous (about 80 sRNAs in E. coli) and play significant functions in the physiology of living organisms, their mechanism of action remains largely unknown. sRNAs are usually non-coding and found in both eukaryotic and prokaryotic organisms. The tremendous potential of sRNAs as modulators of gene expression makes this area of research particularly exciting. RyhB is a sRNA discovered in different bacteria, among them E. coli and several pathogenic species (e.g. K. pneumoniae and Y. pestis). With our work we want to address the unique features of RyhB mechanism; (1) it regulates about 20 mRNAs, which is an unprecedented number of target mRNAs for a single sRNA; (2) it rapidly down-regulates specific mRNAs (sRNA-mediated mRNA decay or sRNA-mmd) by recruiting a multi-protein complex, the RNA degradosome; and (3) it specifically regulates genes involved in iron metabolism.