Biomolecular condensates as organizers of mRNA decay in bacteria

NIH RePORTER · NIH · R01 · $308,164 · view on reporter.nih.gov ↗

Abstract

Despite the absence of organelles, bacteria exhibit an intricate subcellular organization that is required for cells to grow, divide and replicate. A key question is how do simple bacteria go beyond bags of molecules to spatially and temporally organize physiological processes needed to sustain life and regulate development? It has been shown that bacteria achieve subcellular organization using microcompartments, curvature sensing, nucleoid occlusion, and unique lipid and peptidoglycan composition at the cell poles. Liquid-phase separated droplets, termed biomolecular condensates, spatially organize biochemical pathways as membraneless organelles in eukaryotes including P-bodies and stress granules. In collaboration with Jared Schrader's lab, we discovered that ribonuclease Rnase E forms liquid-phase separated bacterial ribonucleoprotein bodies (BR-bodies) that share similarities with P-bodies and stress granules. In this proposal we investigate: 1) the mechanisms that promote Rnase E BR-body formation, 2) mechanisms that regulate selective permeability of BR-bodies to messenger RNA over non-coding RNAs, and 3) the role of Rnase E scaffolding and biomolecular condensation upon mRNA decay. Our studies of BR-bodies will likely provide an illuminating initial example of biomolecular condensates as central organizers of biochemistry within bacteria, and reveal new modes of genetic regulation. This new understanding of mRNA decay should also reveal new insights into regulatory processes that govern bacterial virulence pathways and identify potential antibiotic strategies that disrupt BR-body functions.

Key facts

NIH application ID
10376044
Project number
5R01GM136863-03
Recipient
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Principal Investigator
William Seth Childers
Activity code
R01
Funding institute
NIH
Fiscal year
2022
Award amount
$308,164
Award type
5
Project period
2020-04-21 → 2025-03-31