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


  • eng

Conference Location

  • United States