Structural basis for impaired 5' processing of a mutant tRNA associated with defects in neuronal homeostasis.
Journal Article (Journal Article)
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 tRNAArgUCU 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.
Full Text
Duke Authors
Cited Authors
- Lai, LB; Lai, SM; Szymanski, ES; Kapur, M; Choi, EK; Al-Hashimi, HM; Ackerman, SL; Gopalan, V
Published Date
- March 8, 2022
Published In
Volume / Issue
- 119 / 10
Start / End Page
- e2119529119 -
PubMed ID
- 35238631
Pubmed Central ID
- PMC8915964
Electronic International Standard Serial Number (EISSN)
- 1091-6490
Digital Object Identifier (DOI)
- 10.1073/pnas.2119529119
Language
- eng
Conference Location
- United States