Dataset Information

Ribosomal and tRNA Biogenesis Interact to Control Hypoxic Injury and Translation

ABSTRACT: Protein translation is an essential cellular process, but paradoxically, it can also promote aging and other stresses. In a screen for mutations that protect C. elegans from hypoxic stress, we isolated multiple genes that impact translation, including a ribosomal RNA helicase gene, ddx-52, tRNA biosynthesis genes, and a gene controlling amino acid availability. To better define the mechanisms whereby these genes control hypoxic injury, we performed a second screen for genetic suppressors of the ddx-52(lf) phenotypes. This screen identified multiple genes involved in ribosome biogenesis. Surprisingly, the suppressor mutations were able to restore normal hypoxic sensitivity and protein synthesis to the tRNA biosynthesis mutants, but not to the mutant reducing amino acid uptake. Proteomic characterization of the mutants demonstrated that reduced tRNA biosynthetic activity produces a corresponding reduction in ribosomal structural subunits. Our study uncovers an uncharacterized regulatory interaction between ribosomal biogenesis and tRNA abundance controlling translation and hypoxic survival. A proteomic analysis of a threonyl-tRNA synthetase mutant with and without the ribosomal biogenesis suppressors revealed an uncharacterized feedback mechanism whereby disruption of tRNA aminoacylation results in a corresponding reduction in ribosomal subunits, thereby explaining the ability of enhanced ribosomal biogenesis to suppress reduced tRNA aminoacylation.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Caenorhabditis Elegans

SUBMITTER: Xiaoting Tang

LAB HEAD: James E Bruce

PROVIDER: PXD017267 | Pride | 2022-02-15

REPOSITORIES: pride

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Dataset's files

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			Action	DRS
	0119_N2_0hr_rep1.pep.xml	Pepxml
	0119_N2_0hr_rep1.raw	Raw
	0119_N2_0hr_rep2.pep.xml	Pepxml
	0119_N2_0hr_rep2.raw	Raw
	0119_larp_0hr_rep1.pep.xml	Pepxml

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Publications

Coordinate Regulation of Ribosome and tRNA Biogenesis Controls Hypoxic Injury and Translation.

Itani Omar A OA Zhong Xuefei X Tang Xiaoting X Scott Barbara A BA Yan Jun Yi JY Flibotte Stephane S Lim Yiting Y Hsieh Andrew C AC Bruce James E JE Van Gilst Marc M Crowder C Michael CM

Current biology : CB 20201105 1

The translation machinery is composed of a myriad of proteins and RNAs whose levels must be coordinated to efficiently produce proteins without wasting energy or substrate. However, protein synthesis is clearly not always perfectly tuned to its environment, as disruption of translation machinery components can lengthen lifespan and stress survival. While much has been learned from bacteria and yeast about translational regulation, much less is known in metazoans. In a screen for mutations protec ...[more]

PMID: 33157031

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