Impact of tRNA modifications and tRNA-modifying enzymes on proteostasis and human disease

• Autor(a) principal: Pereira, Marisa
• Data de Publicação: 2018
• Outros Autores: Francisco, Stephany, Varanda, Ana Sofia, Santos, Mafalda, Santos, Manuel A. S., Soares, Ana Raquel
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/27447
• topic: Transfer RNA; tRNA modifications; tRNA-modifying enzymes; Proteostasis; Conformational disorders; Translation; Protein aggregation; Metabolic diseases; Nervous system diseases; Nucleic acid conformation; tRNA methyltransferases; Protein biosynthesis; RNA processing, post-transcriptional

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.