1. Human tRNAs with inosine 34 are essential to efficiently translate eukarya-specific low-complexity proteins
- Author
-
Marina Murillo Recio, Noelia Camacho, Ana Pardo-Saganta, Lluís Ribas de Pouplana, Marina Marcet-Houben, Helena Catena, Adrian Gabriel Torres, Helaine Graziele Santos Vieira, Oscar Reina, Toni Gabaldón, Eva Maria Novoa, Marta Rodríguez-Escribà, Àlbert Rafels-Ybern, Francisco Miguel Torres, and Barcelona Supercomputing Center
- Subjects
Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC] ,AcademicSubjects/SCI00010 ,Adenosine Deaminase ,Protein domain ,Wobble base pair ,Computational biology ,Cell Growth Processes ,Biology ,Proteïnes -- Anàlisi -- Informàtica ,environment and public health ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Protein Domains ,RNA, Transfer ,Genetics ,medicine ,Protein biosynthesis ,RNA and RNA-protein complexes ,Cell Adhesion ,Humans ,RNA, Messenger ,Inosine ,Codon ,Gene ,030304 developmental biology ,Protein Synthesis Inhibitors ,0303 health sciences ,Eukaryota ,Translation (biology) ,tRNAs ,HEK293 Cells ,Codon usage bias ,Protein Biosynthesis ,RNA-protein complexes ,Transfer RNA ,RNA ,Female ,Enzims ,Ribosomes ,Proteïnes ,030217 neurology & neurosurgery ,Genètica ,medicine.drug - Abstract
The modification of adenosine to inosine at the wobble position (I34) of tRNA anticodons is an abundant and essential feature of eukaryotic tRNAs. The expansion of inosine-containing tRNAs in eukaryotes followed the transformation of the homodimeric bacterial enzyme TadA, which generates I34 in tRNAArg and tRNALeu, into the heterodimeric eukaryotic enzyme ADAT, which modifies up to eight different tRNAs. The emergence of ADAT and its larger set of substrates, strongly influenced the tRNA composition and codon usage of eukaryotic genomes. However, the selective advantages that drove the expansion of I34-tRNAs remain unknown. Here we investigate the functional relevance of I34-tRNAs in human cells and show that a full complement of these tRNAs is necessary for the translation of low-complexity protein domains enriched in amino acids cognate for I34-tRNAs. The coding sequences for these domains require codons translated by I34-tRNAs, in detriment of synonymous codons that use other tRNAs. I34-tRNA-dependent low-complexity proteins are enriched in functional categories related to cell adhesion, and depletion in I34-tRNAs leads to cellular phenotypes consistent with these roles. We show that the distribution of these low-complexity proteins mirrors the distribution of I34-tRNAs in the phylogenetic tree. Spanish Ministry of Economy and Competitiveness [PID2019-108037RB-100 to L.R.d.P., PGC2018-099921 to T.G., PGC2018-098152-A-100 to E.M.N]; Australian Research Council [DP180103571 to E.M.N]; European Union's Horizon 2020 research and innovation programme [ERC-2016–724173 to T.G.]. Funding for open access charge: Spanish Ministry of Economy and Competitiveness. Peer Reviewed "Article signat per 14 autors/es: Adrian Gabriel Torres, Marta Rodríguez-Escribà, Marina Marcet-Houben, Helaine Graziele Santos Vieira, Noelia Camacho, Helena Catena, Marina Murillo Recio, Àlbert Rafels-Ybern, Oscar Reina, Francisco Miguel Torres, Ana Pardo-Saganta, Toni Gabaldón, Eva Maria Novoa, Lluís Ribas de Pouplana"
- Published
- 2021