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Title: Impact of tRNA modifications and tRNA-modifying enzymes on proteostasis and human disease
Author: Pereira, Marisa
Francisco, Stephany
Varanda, Ana Sofia
Santos, Mafalda
Santos, Manuel A. S.
Soares, Ana Raquel
Keywords: Transfer RNA
tRNA modifications
tRNA-modifying enzymes
Conformational disorders
Protein aggregation
Metabolic diseases
Nervous system diseases
Nucleic acid conformation
tRNA methyltransferases
Protein biosynthesis
RNA processing, post-transcriptional
Issue Date: Dec-2018
Publisher: MDPI
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.
Peer review: yes
DOI: 10.3390/ijms19123738
ISSN: 1661-6596
Appears in Collections:IBIMED - Artigos
DCM - Artigos

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