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Annual Review of Genomics and Human Genetics

Volume 20, 2019

tRNA Metabolism and Neurodevelopmental Disorders

Abstract

tRNAs are short noncoding RNAs required for protein translation. The human genome includes more than 600 putative tRNA genes, many of which are considered redundant. tRNA transcripts are subject to tightly controlled, multistep maturation processes that lead to the removal of flanking sequences and the addition of nontemplated nucleotides. Furthermore, tRNAs are highly structured and posttranscriptionally modified. Together, these unique features have impeded the adoption of modern genomics and transcriptomics technologies for tRNA studies. Nevertheless, it has become apparent from human neurogenetic research that many tRNA biogenesis proteins cause brain abnormalities and other neurological disorders when mutated. The cerebral cortex, cerebellum, and peripheral nervous system show defects, impairment, and degeneration upon tRNA misregulation, suggesting that they are particularly sensitive to changes in tRNA expression or function. An integrated approach to identify tRNA species and contextually characterize tRNA function will be imperative to drive future tool development and novel therapeutic design for tRNA-associated disorders.

Keyword(s): neurodegeneration, neurodevelopment, oligodendrocyte, sequencing, translation, tRNA
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2019-08-31
2024-04-19
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tRNA Metabolism and Neurodevelopmental Disorders
Annual Review of Genomics and Human Genetics 20, 359 (2019); https://doi.org/10.1146/annurev-genom-083118-015334
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