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TRNA regulation and amino acid usage bias reflect a coordinated metabolic adaptationin Plasmodium falciparum

ABSTRACT: An adaptive feature of malaria-causing parasites is the digestion of host hemoglobin (HB) to acquire amino acids (AAs). Here, we describe a link between nutrient availability and translation dependent regulation of gene expression as an adaptive strategy. We show that tRNA expression in Plasmodium falciparum does not match the decoding need expected for optimal translation. A subset of tRNAs decoding AAs that are insufficiently provided by HB are lowly expressed, wherein the abundance of a protein-coding transcript is negatively correlated with the decoding requirement of these tRNAs. Proliferation-related genes have evolved a high requirement of these tRNAs, thereby proliferation can be modulated by repressing protein synthesis of these genes during nutrient stress. We conclude that the parasite modulates translation elon- gation by maintaining a discordant tRNA profile to exploit variations in AA-composition among genes as an adaptation strategy. This study exemplifies metabolic adaptation as an important driving force for pro- tein evolution.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood

DISEASE(S): Plasmodium Falciparum Malaria

SUBMITTER: Akos Vegvari

LAB HEAD: Akos Vegvari

PROVIDER: PXD056396 | Pride | 2024-11-06

REPOSITORIES: Pride

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			Action	DRS
	20220329_HF2_03_PB_149_SC_2_TMT8.raw	Raw
	20220407_SherwinChan_SC_2_New_TMT8.xlsx	Xlsx

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tRNA regulation and amino acid usage bias reflect a coordinated metabolic adaptation in Plasmodium falciparum [RNA-Seq III]

Project description:An adaptive feature of malaria-causing parasites is the digestion of host hemoglobin (HB) to acquire amino acids (AAs). Here we describe a link between nutrient availability and translation dependent regulation of gene expression as an adaptive strategy. We show that tRNA expression in Plasmodium falciparum does not match the decoding need expected for optimal translation. A subset of tRNAs decoding AAs that are insufficiently provided by HB are lowly expressed, wherein the abundance of a protein-coding transcript is negatively correlated with the decoding requirement of these tRNAs. Proliferation-related genes have evolved a high requirement of these tRNAs, thereby proliferation can be modulated by repressing protein synthesis of these genes during nutrient stress. We conclude that the parasite modulates translation elongation by maintaining a discordant tRNA profile to exploit variations in AA-composition among genes as an adaptation strategy. This study exemplifies metabolic adaptation as an important driving force for protein evolution.

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