PXD024527

PXD024527 is an original dataset announced via ProteomeXchange.

Title	Phe-tRNA aminoacylation is disrupted by C4G2 repeat RNA C9orf72mutation associated with ALS and FTD
Description	Expanded hexanucleotide GGGGCC repeat mutation in the C9orf72 gene is the main genetic cause of neurodegenerative diseases amyotrophic lateral sclerosis and frontotemporal dementia. Sense and antisense transcripts of the repeats form nuclear RNA foci and bind various RNA binding proteins. Sequestration of these proteins is predicted to be cytotoxic. In this study we identified proteins that bind to antisense repeat RNA with RNA pull-down assay in combination with mass spectrometry. The interactions were confirmed in human brain lysates. Among interacting proteins is phenylalanine-tRNA synthetase (FARS). We confirmed interaction with FARS in C9orf72 mutation-positive patient-derived cells with RNA fluorescent in situ hybridization in combination with immunocytochemistry and with RNA-protein proximity ligation assay. We predict this interaction impacts the function of FARS as we observed decreased levels of charged Phe-tRNA in C9orf72 mutation-positive patient-derived cells compared to control. This study shows that antisense RNA interaction with FARS could influence protein synthesis and reveals so far unknown connection between RNA repeats and aminoacil tRNA synthetases in C9orf72 mutation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:55:05.866.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD024527
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Xiaoke Yin
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-04 08:41:04	ID requested
1	2023-09-18 02:12:36	announced
⏵ 2	2023-11-14 08:55:06	announced	2023-11-14: Updated project metadata.

10.6019/PXD024527;

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

Manuel Mayr
contact affiliation	King’s BHF Centre, King’s College London, London, UK
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. PXD024527
     1. Label: PRIDE project
     2. Name: Phe-tRNA aminoacylation is disrupted by C4G2 repeat RNA C9orf72mutation associated with ALS and FTD