PXD024075-1

PXD024075 is an original dataset announced via ProteomeXchange.

Title	Synaptic accumulation of FUS triggers early misregulation of synaptic RNAs in ALS-FUS mice
Description	Mutations disrupting the nuclear localization of the RNA-binding protein FUS characterize a subset of amyotrophic lateral sclerosis patients (ALS-FUS). FUS regulates nuclear RNAs, but its role at the synapse is poorly understood. Using super-resolution imaging we determined that the localization of FUS within synapses occurs predominantly near the vesicle reserve pool of presynaptic sites. Using CLIP-seq on synaptoneurosomes, we identified synaptic FUS RNA targets, encoding proteins associated with synapse organization and plasticity. Significant increase of synaptic FUS during early disease in a knock-in mouse model of ALS-FUS was accompanied by alterations in density and size of GABAergic synapses. mRNAs abnormally accumulated at the synapses of 6-month-old ALS-FUS mice were enriched for FUS targets and correlated with those depicting increased short-term mRNA stability via binding primarily on multiple exonic sites. Our study indicates that synaptic FUS accumulation in early disease leads to synaptic impairment, potentially representing an initial trigger of neurodegeneration.
HostingRepository	PRIDE
AnnounceDate	2021-05-05
AnnouncementXML	Submission_2021-05-04_22:20:15.267.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Katharina Hembach
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-08 22:48:48	ID requested
⏵ 1	2021-05-04 22:20:15	announced

Dataset with its publication pending

submitter keyword: mouse, cortex, FUS, ALS, neurodegeneration, synaptoneurosomes, Orbitrap, label-free quantification

Magdalini Polymenidou
contact affiliation	Department of Quantitative Biomedicine, University of Zurich, Switzerland
contact email	magdalini.polymenidou@uzh.ch
lab head
Katharina Hembach
contact affiliation	Department of Quantitative Biomedicine, University of Zurich
contact email	katharina.hembach@gmail.com
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/2021/05/PXD024075

PRIDE project URI

• PRIDE
  1. PXD024075
     1. Label: PRIDE project
     2. Name: Synaptic accumulation of FUS triggers early misregulation of synaptic RNAs in ALS-FUS mice