Impact of tRNA Modifications and tRNA-Modifying Enzymes on Proteostasis and Human Disease.
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.
['Pereira|Marisa|M|', 'Francisco|Stephany|S|', 'Varanda|Ana Sofia|AS|', 'Santos|Mafalda|M|0000-0001-8102-3287', 'Santos|Manuel A S|MAS|', 'Soares|Ana Raquel|AR|0000-0003-4000-7461']
D000818:Animals D004248:DNA (Cytosine-5-)-Methyltransferases D006801:Humans D008659:Metabolic Diseases D009422:Nervous System Diseases D009690:Nucleic Acid Conformation D066329:Protein Aggregates D014176:Protein Biosynthesis D000074702:Proteostasis D012323:RNA Processing, Post-Transcriptional D012343:RNA, Transfer D014452:Ubiquitins D012359:tRNA Methyltransferases
tRNA modifications tRNA-modifying enzymes proteostasis transfer RNA translation protein aggregation conformational disorders