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A role for tRNA modifications in the expansion of proteome diversity

ABSTRACT: The mechanisms that drive the evolution of proteome diversity are poorly understood. Here we investigate the functional significance of eight eukaryotic tRNAs that contain inosine in the wobble position of the anticodon (I34-tRNAs). We find that these modified tRNAs are essential to translate a subset of the eukaryotic proteome composed of eukaryote-specific, low-complexity polypeptides involved in interactions with the extracellular environment, including proteins containing mucin-like domains. Depletion of I34-tRNAs in human cells leads to impaired translation of these proteins, and morphological and cell adhesion phenotypes. We further show that translation defects are strictly dependent on codon distribution and composition of transcripts. Genes coding for the precursors of I34-tRNAs are almost absent in prokaryotes and abundant in eukaryotes. We conclude that I34-tRNAs bestowed eukaryotes with the ability to expand their proteomes with a new set of highly-biased genetic sequences that provided these organisms with novel extracellular functionalities.

ORGANISM(S): Homo sapiens

PROVIDER: GSE150860 | GEO | 2021/06/28

REPOSITORIES: GEO

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