PXD014085

PXD014085 is an original dataset announced via ProteomeXchange.

Title	Impact of oligoarginine peptides in RNA-binding proteomes
Description	Expanded intronic GGGGCC repeats in C9ORF72 produce several dipeptides, from which the two that contain arginine, (PR)n and (GR)n, accumulate at nucleoli and kill cells. While this toxicity plays an important role in ALS pathogenesis, its mechanism remains unknown. We here show that PR dipeptides bind avidly to DNA and RNA, so that any cellular reaction involving nucleic acids is impaired by the dipeptides. Consistently, PR-induced cell death can be rescued by addition of non-coding oligonucleotides. Interestingly, the effects of PR dipeptides are to a large extent mimicked by protamine, a sperm-specific Arg-rich protein, and the toxicity of either protamine or PR dipeptides is rescued by the anticoagulant heparin. We propose that the generalized coating of nucleic acids by Arg-rich peptides accounts for the toxicity of C9ORF72 mutations in ALS.
HostingRepository	PRIDE
AnnounceDate	2021-04-12
AnnouncementXML	Submission_2021-04-12_08:04:33.633.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eduardo Zarzuela
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-31 03:53:25	ID requested
⏵ 1	2021-04-12 08:04:33	announced

Dataset with its publication pending

submitter keyword: ALS, Label Free, PR20, HF, Ribosome Binding Proteins

Javier Muñoz
contact affiliation	CNIO
contact email	jmunozpe@cnio.es
lab head
Eduardo Zarzuela
contact affiliation	Centro Nacional de Investigaciones Oncológicas
contact email	eduzarfer@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014085
     1. Label: PRIDE project
     2. Name: Impact of oligoarginine peptides in RNA-binding proteomes