Starvation sensing by mycobacterial RelA/SpoT homologue through constitutive surveillance of translation.

Autor: Li Y; Division of Genetics, New York State Department of Health, Wadsworth Center, Albany, NY 12208., Majumdar S; Division of Translational Medicine, New York State Department of Health, Wadsworth Center, Albany, NY 12237., Treen R; Division of Genetics, New York State Department of Health, Wadsworth Center, Albany, NY 12208.; Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, NY 12208., Sharma MR; Division of Translational Medicine, New York State Department of Health, Wadsworth Center, Albany, NY 12237., Corro J; Division of Genetics, New York State Department of Health, Wadsworth Center, Albany, NY 12208.; Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, NY 12208., Gamper HB; Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107., Manjari SR; Division of Translational Medicine, New York State Department of Health, Wadsworth Center, Albany, NY 12237., Prusa J; Department of Molecular Microbiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110., Banavali NK; Division of Translational Medicine, New York State Department of Health, Wadsworth Center, Albany, NY 12237., Stallings CL; Department of Molecular Microbiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110., Hou YM; Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107., Agrawal RK; Division of Translational Medicine, New York State Department of Health, Wadsworth Center, Albany, NY 12237.; Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, NY 12208., Ojha AK; Division of Genetics, New York State Department of Health, Wadsworth Center, Albany, NY 12208.; Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, NY 12208.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 May 30; Vol. 120 (22), pp. e2302006120. Date of Electronic Publication: 2023 May 22.
DOI: 10.1073/pnas.2302006120
Abstrakt: The stringent response, which leads to persistence of nutrient-starved mycobacteria, is induced by activation of the RelA/SpoT homolog (Rsh) upon entry of a deacylated-tRNA in a translating ribosome. However, the mechanism by which Rsh identifies such ribosomes in vivo remains unclear. Here, we show that conditions inducing ribosome hibernation result in loss of intracellular Rsh in a Clp protease-dependent manner. This loss is also observed in nonstarved cells using mutations in Rsh that block its interaction with the ribosome, indicating that Rsh association with the ribosome is important for Rsh stability. The cryo-EM structure of the Rsh-bound 70S ribosome in a translation initiation complex reveals unknown interactions between the ACT domain of Rsh and components of the ribosomal L7/L12 stalk base, suggesting that the aminoacylation status of A-site tRNA is surveilled during the first cycle of elongation. Altogether, we propose a surveillance model of Rsh activation that originates from its constitutive interaction with the ribosomes entering the translation cycle.
Databáze: MEDLINE
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