Datasets

Title	Ribosome Profiling in Isoleucine tRNA Isoswitch Cells
Organism
Number of Samples	8
Release Date	2021/04/19 00:00
Sequencing Types
Protocol Details

Title
Authors	Earnest-Noble LB,Hsu D,Chen S,Asgharian H,Nandan M,Passarelli MC,Goodarzi H,Tavazoie SF
Journal	Nature cancer
Publication Date	2022 Dec
Abstract	The human genome contains 61 codons encoding 20 amino acids. Synonymous codons representing a given amino acid are decoded by a set of transfer RNAs (tRNAs) called isoacceptors. We report the surprising observation that two isoacceptor tRNAs that decode synonymous codons become modulated in opposing directions during breast cancer progression. Specifically, tRNA Ile UAU became upregulated, whereas tRNA Ile GAU became repressed as breast cancer cells attained enhanced metastatic capacity. Functionally, tRNA Ile UAU promoted and tRNA Ile GAU suppressed metastatic colonization in mouse xenograft models. These tRNAs mediated opposing effects on codon-dependent translation of growth-promoting genes, consistent with genomic enrichment or depletion of their cognate codons in mitotic genes. Our findings uncover a specific isoacceptor tRNA pair that act in opposition, divergently impacting growth-regulating genes and a disease phenotype. Degeneracy of the genetic code can thus be biologically exploited by human cancer cells via tRNA isoacceptor shifts that causally facilitate the transition toward a growth-promoting state. © 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
PMC
PMID	36510010
DOI

Earnest-Noble et al. 2023 (PRJNA723012)