Structural basis for impaired 5' processing of a mutant tRNA associated with defects in neuronal homeostasis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35238631.
- Also identified by DOI 10.1073/pnas.2119529119 and PMC identifier 8915964.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
SignificanceUnderstanding and treating neurological disorders are global priorities. Some of these diseases are engendered by mutations that cause defects in the cellular synthesis of transfer RNAs (tRNAs), which function as adapter molecules that translate messenger RNAs into proteins. During tRNA biogenesis, ribonuclease P catalyzes removal of the transcribed sequence upstream of the mature tRNA. Here, we focus on a cytoplasmic tRNA<sup>Arg</sup><sub>UCU</sub> that is expressed specifically in neurons and, when harboring a particular point mutation, contributes to neurodegeneration in mice. Our results suggest that this mutation favors stable alternative structures that are not cleaved by mouse ribonuclease P and motivate a paradigm that may help to understand the molecular basis for disease-associated mutations in other tRNAs.
Medical subject headings
- Homeostasis
- Neurons
- Nucleic Acid Conformation
- RNA, Transfer