title: Genome recoding by tRNA modifications.
abstract: RNA modifications are emerging as an additional regulatory layer on top of the primary RNA sequence. These modifications are particularly enriched in tRNAs where they can regulate not only global protein translation, but also protein translation at the codon level. Modifications located in or in the vicinity of tRNA anticodons are highly conserved in eukaryotes and have been identified as potential regulators of mRNA decoding. Recent studies have provided novel insights into how these modifications orchestrate the speed and fidelity of translation to ensure proper protein homeostasis. This review highlights the prominent modifications in the tRNA anticodon loop: queuosine, inosine, 5-methoxycarbonylmethyl-2-thiouridine, wybutosine, threonyl-carbamoyl-adenosine and 5-methylcytosine. We discuss the functional relevance of these modifications in protein translation and their emerging role in eukaryotic genome recoding during cellular adaptation and disease.
authors.affiliation: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Tuorto
authors.affiliation: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany f.lyko@dkfz.de.
authors.forename: Frank
authors.identifier: 0000-0002-4873-5431
authors.initials: F
authors.lastname: Lyko
mesh_terms: D044503:5-Methylcytosine / Q000737:chemistry; D000818:Animals; D000926:Anticodon / Q000737:chemistry* / Q000235:genetics; D056890:Eukaryota / Q000235:genetics; D019143:Evolution, Molecular; D016678:Genome; D006801:Humans; D007288:Inosine / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009704:Nucleoside Q / Q000737:chemistry; D009705:Nucleosides / Q000737:chemistry; D014176:Protein Biosynthesis; D012343:RNA, Transfer / Q000737:chemistry* / Q000235:genetics*; D013891:Thiouridine / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: C011701:5-carbomethoxymethyl-2-thiouridine; D000926:Anticodon; D009705:Nucleosides; C467591:wybutosine; D013891:Thiouridine; D009704:Nucleoside Q; D007288:Inosine; D044503:5-Methylcytosine; D012343:RNA, Transfer
keywords: genome recoding; protein translation; tRNA anticodon; tRNA modification