PXD022604

PXD022604 is an original dataset announced via ProteomeXchange.

Title	Reactive astrocytes in ALS display dysregulated intron retention
Description	Reactive astrocytes are implicated in amyotrophic lateral sclerosis (ALS), although the mechanisms controlling reactive transformation are unknown. We show that decreased intron retention (IR) is common to human iPSC-derived astrocytes carrying VCP, C9orf72 and SOD1 ALS-causing mutations as well as astrocytes stimulated to undergo reactive transformation. Notably, transcripts with decreased IR and increased expression are overrepresented in reactivity processes including cell-adhesion, stress-response, and immune-activation. We examined translatome sequencing (TRAP-seq) of astrocytes from a SOD1 mouse model, which revealed that transcripts upregulated in translation significantly overlap with transcripts with decreased IR. Using nucleo-cytoplasmic fractionation of VCP astrocytes coupled with mRNA sequencing and proteomics, we identify that decreased IR in nuclear-detained transcripts is associated with increased cytoplasmic expression of genes and proteins encoding regulators of reactivity - indicating nuclear-to-cytoplasmic translocation and translation of spliced reactivity-related transcripts. Our study provides important insights into the molecular regulation of reactive transformation of ALS astrocytes.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_14:01:37.102.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Oliver Ziff
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-18 06:17:04	ID requested
⏵ 1	2021-09-09 14:01:37	announced

Ziff OJ, Taha DM, Crerar H, Clarke BE, Chakrabarti AM, Kelly G, Neeves J, Tyzack GE, Luscombe NM, Patani R, Reactive astrocytes in ALS display diminished intron retention. Nucleic Acids Res, 49(6):3168-3184(2021) [pubmed]

submitter keyword: Alternative splicing, intron retention, astrocytes, amyotrophic lateral sclerosis, motor neuron disease, neurodegeneration, reactive astrocytes, human induced pluripotent stem cell, RNA sequencing, transcriptome profiling

Rickie Patani
contact affiliation	The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK Department of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK
contact email	rickie.patani@ucl.ac.uk
lab head
Oliver Ziff
contact affiliation	University College London
contact email	ojziff@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/2021/09/PXD022604

PRIDE project URI

• PRIDE
  1. PXD022604
     1. Label: PRIDE project
     2. Name: Reactive astrocytes in ALS display dysregulated intron retention