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Duplicated ribosomal protein paralogs promote alternative translation and drug resistance

ABSTRACT: Ribosomes are often seen as monolithic machines produced from uniformly regulated genes. However, in yeast most ribosomal proteins come from duplicated genes. Here, we demonstrate that gene duplication may serve as a stress-adaptation mechanism modulating the global proteome through the differential expression of ribosomal protein paralogs. Our data indicate that the yeast paralog pair of the ribosomal protein L7/uL30 produces two differentially acetylated proteins. Under normal conditions most ribosomes incorporate the hypo-acetylated major form favoring the translation of genes with short open reading frames. Exposure to drugs, on the other hand, increases the production of ribosomes carrying the hyper-acetylated minor paralog that increases translation of long open reading frames. Many of these paralogs dependent genes encode cell wall proteins that could promote tolerance to drugs as their translation increases after exposure to drugs. Together the data reveal a mechanism of translation control through the differential use of near-identical ribosomal protein isoforms.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Mathieu Catala

LAB HEAD: Sherif Abou Elela

PROVIDER: PXD033843 | Pride | 2022-08-09

REPOSITORIES: Pride

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			Action	DRS
	517Mathieu_L7_AA_LysC.raw	Raw
	517Mathieu_L7_BB_LysC.raw	Raw
	520Mathieu_2_AA_LysC.raw	Raw
	520Mathieu_2_BB_LysC.raw	Raw
	524Mathieu_MC1.raw	Raw

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Duplicated ribosomal protein paralogs promote alternative translation and drug resistance

Project description:Ribosomes are often seen as monolithic machines produced from uniformly regulated genes. However, in yeast most ribosomal proteins come from duplicated genes. Here, we demonstrate that gene duplication may serve as an adaption mechanism modulating the global proteome through the differential expression of ribosomal proteins paralogs after exposure to stress. Our data indicate that the yeast paralog pair of the ribosomal protein L7/uL30 produces two differentially acetylated proteins. Under normal conditions most ribosomes incorporate the hypo-acetylated major form favoring the translation of genes with short open reading frames. Exposure to drugs, on the other hand, increases the production of ribosomes carrying the hyper-acetylated minor paralog that increases translation of long reading frames. Many of these long genes encode cell wall proteins that increase drug resistance in a programed change in translation equilibrium. Together the data reveal a mechanism of translation control through the differential fates of near-identical ribosomal protein isoforms.

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