PXD042474

PXD042474 is an original dataset announced via ProteomeXchange.

Title	Phenylalanine-tRNA aminoacylation is compromised by ALS/FTD-associated C9orf72 C4G2 repeat RNA
Description	The expanded hexanucleotide GGGGCC repeat mutation in the C9orf72 gene is the main genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Under one disease mechanism, sense and antisense transcripts of the repeat are predicted to bind various RNA-binding proteins, compromise their function and cause cytotoxicity. Focusing on cytoplasmic interaction of the CCCCGG antisense repeat RNA this study identifies phenylalanine-tRNA synthetase (FARS) subunit alpha (FARSA) as the main interactor. The aminoacylation of tRNAPhe by FARS is inhibited by antisense RNA, leading to decreased levels of charged tRNAPhe. Remarkably, this is associated with global reduction of phenylalanine incorporation in the proteome and significant decrease in expression of phenylalanine-rich proteins in cellular models and patient tissues. In conclusion, this research reveals functional inhibition of FARSA in the presence of antisense RNA repeats. Compromised aminoacylation of tRNA could lead to impairments in protein synthesis and further contribute to C9orf72 mutation-associated pathology.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:55:06.971.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD042474
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Xiaoke Yin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-24 08:04:18	ID requested
1	2023-09-18 02:17:45	announced
⏵ 2	2023-11-14 08:55:07	announced	2023-11-14: Updated project metadata.

10.6019/PXD042474;

submitter keyword: antisense RNA, phenylalanine-tRNA synthetase, frontotemporal dementia,amyotrophic lateral sclerosis, C9orf72 mutation

Manuel Mayr
contact affiliation	King's College London
contact email	manuel.mayr@kcl.ac.uk
lab head
Xiaoke Yin
contact affiliation	Cardiovascular Division, King's College London
contact email	xiaoke.yin@kcl.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042474
     1. Label: PRIDE project
     2. Name: Phenylalanine-tRNA aminoacylation is compromised by ALS/FTD-associated C9orf72 C4G2 repeat RNA