{"title":"tRNA Dysregulation in Neurodevelopmental and Neurodegenerative Diseases.","authors":"Robert W Burgess, Erik Storkebaum","doi":"10.1146/annurev-cellbio-021623-124009","DOIUrl":null,"url":null,"abstract":"<p><p>Transfer RNAs (tRNAs) decode messenger RNA codons to peptides at the ribosome. The nuclear genome contains many tRNA genes for each amino acid and even each anticodon. Recent evidence indicates that expression of these tRNAs in neurons is regulated, and they are not functionally redundant. When specific tRNA genes are nonfunctional, this results in an imbalance between codon demand and tRNA availability. Furthermore, tRNAs are spliced, processed, and posttranscriptionally modified. Defects in these processes lead to neurological disorders. Finally, mutations in the aminoacyl tRNA synthetases (aaRSs) also lead to disease. Recessive mutations in several aaRSs cause syndromic disorders, while dominant mutations in a subset of aaRSs lead to peripheral neuropathy, again due to an imbalance between tRNA supply and codon demand. While it is clear that disrupting tRNA biology often leads to neurological disease, additional research is needed to understand the sensitivity of neurons to these changes.</p>","PeriodicalId":7944,"journal":{"name":"Annual review of cell and developmental biology","volume":null,"pages":null},"PeriodicalIF":11.4000,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of cell and developmental biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1146/annurev-cellbio-021623-124009","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/6/20 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 3
Abstract
Transfer RNAs (tRNAs) decode messenger RNA codons to peptides at the ribosome. The nuclear genome contains many tRNA genes for each amino acid and even each anticodon. Recent evidence indicates that expression of these tRNAs in neurons is regulated, and they are not functionally redundant. When specific tRNA genes are nonfunctional, this results in an imbalance between codon demand and tRNA availability. Furthermore, tRNAs are spliced, processed, and posttranscriptionally modified. Defects in these processes lead to neurological disorders. Finally, mutations in the aminoacyl tRNA synthetases (aaRSs) also lead to disease. Recessive mutations in several aaRSs cause syndromic disorders, while dominant mutations in a subset of aaRSs lead to peripheral neuropathy, again due to an imbalance between tRNA supply and codon demand. While it is clear that disrupting tRNA biology often leads to neurological disease, additional research is needed to understand the sensitivity of neurons to these changes.
期刊介绍:
The Annual Review of Cell and Developmental Biology, established in 1985, comprehensively addresses major advancements in cell and developmental biology. Encompassing the structure, function, and organization of cells, as well as the development and evolution of cells in relation to both single and multicellular organisms, the journal explores models and tools of molecular biology. As of the current volume, the journal has transitioned from gated to open access through Annual Reviews' Subscribe to Open program, making all articles published under a CC BY license.