PXD021320

PXD021320 is an original dataset announced via ProteomeXchange.

Title	AltFUS interactome from mitochondrial extracts
Description	Novel functional coding sequences (altORFs) are camouflaged within annotated ones (CDS) in a different reading frame. We discovered an altORF nested in the FUS CDS encoding a conserved 170 amino acid protein, altFUS. AltFUS is endogenously expressed in human tissues, notably in the motor cortex and motor neurons. Overexpression of wild-type FUS and/or amyotrophic lateral sclerosis-linked FUS mutants is known to trigger toxic mechanisms in different models. These include an inhibition of autophagy, loss of mitochondrial potential, and accumulation of cytoplasmic aggregates. We show here that altFUS, not FUS, is responsible for the inhibition of autophagy. AltFUS is also pivotal in the mechanisms leading to the mitochondrial potential loss and accumulation of cytoplasmic aggregates. Suppression of altFUS expression in a Drosophila model of FUS-related toxicity protects against neurodegeneration. Some mutations found in ALS patients are overlooked because of their synonymous effect on the FUS protein. Yet we showed they exert a deleterious effect via their missense consequence on the overlapping altFUS protein. These findings demonstrate that FUS is a bicistronic gene and suggest that both proteins, FUS and altFUS, cooperate in toxic mechanisms.
HostingRepository	PRIDE
AnnounceDate	2020-10-12
AnnouncementXML	Submission_2020-10-12_06:19:15.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marie A Brunet
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-04 08:23:30	ID requested
⏵ 1	2020-10-12 06:19:15	announced

Dataset with its publication pending

submitter keyword: AltFUS, alternative protein

Roucou Xavier
contact affiliation	Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Canada
contact email	xavier.roucou@usherbrooke.ca
lab head
Marie A Brunet
contact affiliation	University of Sherbrooke
contact email	marie.brunet@usherbrooke.ca
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/10/PXD021320

PRIDE project URI

• PRIDE
  1. PXD021320
     1. Label: PRIDE project
     2. Name: AltFUS interactome from mitochondrial extracts