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Structural basis for impaired 5' processing of a mutant tRNA associated with defects in neuronal homeostasis
- Source :
- Proceedings of the National Academy of Sciences of the United States of America, vol 119, iss 10
- Publication Year :
- 2022
-
Abstract
- Significance Understanding 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 Arg UCU 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.
- Subjects :
- Models, Molecular
conformational toggling
tRNA-Arg-TCT-4-1
Ribonuclease P
Substrate Specificity
Mice
RNA, Transfer
Models
Genetics
2.1 Biological and endogenous factors
Animals
Homeostasis
Point Mutation
Magnesium
Aetiology
Base Pairing
Protein Processing
Cerebral Cortex
Neurons
Multidisciplinary
Post-Translational
neurodegeneration
Neurosciences
Molecular
Transfer
Neurological
tRNA processing
RNA
Nucleic Acid Conformation
Protein Processing, Post-Translational
Subjects
Details
- ISSN :
- 10916490
- Volume :
- 119
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....26b77e97535501754e746664c371a233