PXD019596 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-06-04 22:35:28 | ID requested | |
⏵ 1 | 2020-10-27 00:17:11 | announced | |
Publication List
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] |
Keyword List
submitter keyword: Motoneurons, FUS protein,VCP |
ASAP1 |
3’UTR |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD019596
- Label: PRIDE project
- Name: Proteomics analysis of FUS mutant human motoneurons reveals altered regulation of cytoskeleton and other ALS-linked proteins via 3’UTR binding