PXD019596

PXD019596 is an original dataset announced via ProteomeXchange.

Title	Proteomics analysis of FUS mutant human motoneurons reveals altered regulation of cytoskeleton and other ALS-linked proteins via 3’UTR binding
Description	Increasing evidence suggests that in Amyotrophic Lateral Sclerosis (ALS) mutated RNA binding proteins acquire aberrant functions, leading to altered RNA metabolism with significant impact on encoded protein levels. Here, by taking advantage of a human induced Pluripotent Stem Cell (hiPSC)-based model, we aimed to gain insights on the impact of ALS mutant FUS on the motoneuron proteome. Label-free proteomics analysis by mass-spectrometry revealed upregulation of proteins involved in catabolic processes and oxidation-reduction, and downregulation of cytoskeletal proteins and factors directing neuron projection. Mechanistically, proteome alteration does not correlate with transcriptome changes. Rather, we observed a strong correlation with selective binding of mutant FUS to target mRNAs in their 3’UTR. Novel validated targets, selectively bound by mutant FUS only, include genes previously involved in familial or sporadic ALS, such as VCP, and regulators of membrane trafficking and cytoskeleton remodeling, such as ASAP1. These findings unveil a novel mechanism by which mutant FUS might intersect other pathogenic pathways in ALS patients’ motoneurons.
HostingRepository	PRIDE
AnnounceDate	2020-10-27
AnnouncementXML	Submission_2020-10-27_00:17:10.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrea Armirotti
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-04 22:35:28	ID requested
⏵ 1	2020-10-27 00:17:11	announced

Garone MG, Alfano V, Salvatori B, Braccia C, Peruzzi G, Colantoni A, Bozzoni I, Armirotti A, Rosa A, Proteomics analysis of FUS mutant human motoneurons reveals altered regulation of cytoskeleton and other ALS-linked proteins via 3'UTR binding. Sci Rep, 10(1):11827(2020) [pubmed]

submitter keyword: Motoneurons, FUS protein,VCP

ASAP1

3’UTR

Andrea Armirotti
contact affiliation	Analytical Chemistry Lab Fondazione Istituto Italiano di Tecnologia Via Morego 30, 16163 Genova Italy
contact email	andrea.armirotti@iit.it
lab head
Andrea Armirotti
contact affiliation	Analytical Chemistry Lab, Fondazione Istituto Italiano di Tecnologia
contact email	andrea.armirotti@iit.it
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/PXD019596

PRIDE project URI

• PRIDE
  1. PXD019596
     1. Label: PRIDE project
     2. Name: Proteomics analysis of FUS mutant human motoneurons reveals altered regulation of cytoskeleton and other ALS-linked proteins via 3’UTR binding