RNase E and HupB dynamics foster mycobacterial cell homeostasis and fitness

Anna Griego (1) , Thibaut Douché (2) , Quentin Giai Gianetto (2, 3) , Mariette Matondo (2) , Giulia Manina (1)

1 Individualité microbienne et infection - Microbial Individuality and Infection
2 UTechS MSBio - Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology
3 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB

RNA turnover is a primary source of gene expression variation, in turn promoting cellular adaptation. Mycobacteria leverage reversible mRNA stabilization to endure hostile conditions. Although RNase E is essential for RNA turnover in several species, its role in mycobacterial single-cell physiology and functional phenotypic diversification remains unexplored. Here, by integrating live-single-cell and quantitative-mass-spectrometry approaches, we show that RNase E forms dynamic foci, which are associated with cellular homeostasis and fate, and we discover a versatile molecular interactome. We show a likely interaction between RNase E and the nucleoid-associated protein HupB, which is particularly pronounced during drug treatment and infection, where phenotypic diversity increases. Disruption of RNase E expression affects HupB levels, impairing Mycobacterium tuberculosis growth homeostasis during treatment, intracellular replication, and host spread. Our work lays the foundation for targeting the RNase E and its partner HupB, aiming to undermine M. tuberculosis cellular balance, diversification capacity, and persistence.

Domains: Life Sciences [q-bio]; Biochemistry, Molecular Biology; Structural Biology [q-bio.BM]

Anna Griego, Thibaut Douché, Quentin Giai Gianetto, Mariette Matondo, Giulia Manina. RNase E and HupB dynamics foster mycobacterial cell homeostasis and fitness. iScience, 2022, 25 (5), pp.104233. ⟨10.1016/j.isci.2022.104233⟩. ⟨pasteur-03693876⟩