Abstract
Transfer RNAs (tRNAs) are key players of protein synthesis, as they decode the genetic information organized in mRNA codons, translating them into the code of 20 amino acids. To be fully active, tRNAs undergo extensive post-transcriptional modifications, catalyzed by different tRNA-modifying enzymes. Lack of these modifications increases the level of missense errors and affects codon decoding rate, contributing to protein aggregation with deleterious consequences to the cell. Recent works show that tRNA hypomodification and tRNA-modifying-enzyme deregulation occur in several diseases where proteostasis is affected, namely, neurodegenerative and metabolic diseases. In this review, we discuss the recent findings that correlate aberrant tRNA modification with proteostasis imbalances, in particular in neurological and metabolic disorders, and highlight the association between tRNAs, their modifying enzymes, translational decoding, and disease onset.
Highlights
Transfer RNAs are the main players of translation machinery, carrying the amino acids required for nascent peptides being formed at the ribosome [1]
Several genetic mutations in Transfer RNAs (tRNAs)-modifying enzymes have been associated with pathological conditions, in particular, neurological and metabolic disorders, suggesting that hypomodification of tRNAs contribute to the onset and/or development of human diseases (Figure 3/Table 1)
Recent advances in the role of the Elongator complex in the development of neurological disorders has been crucial to highlight the importance of tRNA modifications in proteostasis and human disease
Summary
Transfer RNAs (tRNAs) are the main players of translation machinery, carrying the amino acids required for nascent peptides being formed at the ribosome [1]. TRNALys(UUU), tRNAGln(UUG), and tRNAGlu(UUC), a 2-thio group is added by ubiquitin-ligase-like proteins, namely, Urm, Uba, Ncs, and Ncs, resulting in 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2) [16] (Figure 1) These modifications have been consistently correlated with translational fidelity and proteostasis [14,16,17,18,19,20,21]. Recent developments in next-generation sequencing [38], mass spectrometry [39], and ribosome profiling [40] have enabled the assessment and quantification of tRNA modifications and amino acid misincorporation [41,42], as well as its correlation with translation efficiency. We highlight the association between tRNAs, their modifying enzymes and translation fidelity, and explore their therapeutic potential
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
