PXD022604 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-11-18 06:17:04 | ID requested | |
⏵ 1 | 2021-09-09 14:01:37 | announced | |
Publication List
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] |
Keyword List
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 |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD022604
- Label: PRIDE project
- Name: Reactive astrocytes in ALS display dysregulated intron retention