Burgess Robert W, Storkebaum Erik
The Jackson Laboratory, Bar Harbor, Maine, USA; email:
Donders Institute for Brain, Cognition, and Behavior, Radboud University, Nijmegen, The Netherlands; email:
Annu Rev Cell Dev Biol. 2023 Oct 16;39:223-252. doi: 10.1146/annurev-cellbio-021623-124009. Epub 2023 Jun 20.
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.
转运核糖核酸（tRNA）在核糖体处将信使核糖核酸密码子解码为肽链。核基因组针对每种氨基酸甚至每个反密码子都包含许多tRNA基因。最近的证据表明，这些tRNA在神经元中的表达受到调控，并且它们在功能上并非冗余。当特定的tRNA基因失去功能时，这会导致密码子需求与tRNA可用性之间的失衡。此外，tRNA会进行剪接、加工和转录后修饰。这些过程中的缺陷会导致神经疾病。最后，氨酰tRNA合成酶（aaRS）中的突变也会导致疾病。几种aaRS中的隐性突变会导致综合征性疾病，而一部分aaRS中的显性突变会导致周围神经病变，同样是由于tRNA供应与密码子需求之间的失衡。虽然很明显破坏tRNA生物学通常会导致神经疾病，但仍需要更多研究来了解神经元对这些变化的敏感性。
