PXD009969-1

PXD009969 is an original dataset announced via ProteomeXchange.

Title	RNA instability in amyotrophic lateral sclerosis
Description	Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share key features, including accumulation of the RNA binding protein TDP-43. TDP-43 regulates RNA homeostasis, but it remains unclear whether RNA stability is affected in these disorders. We use Bru-seq and BruChase-seq to assess genome-wide RNA stability in ALS patient-derived cells, demonstrating profound destabilization of ribosomal and mitochondrial transcripts. This pattern is recapitulated by TDP-43 overexpression, suggesting a primary role for TDP-43 in RNA destabilization, and in post-mortem samples from ALS and FTD patients. Proteomics and functional studies illustrate corresponding reductions in mitochondrial components and compensatory increases in protein synthesis. Collectively, these observations suggest that TDP-43 deposition leads to targeted RNA instability in ALS and FTD, and may ultimately cause cell death by disrupting energy production and protein synthesis pathways.
HostingRepository	PRIDE
AnnounceDate	2018-07-24
AnnouncementXML	Submission_2018-07-24_09:46:42.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sami Barmada
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-30 15:57:20	ID requested
⏵ 1	2018-07-24 09:46:44	announced
2	2024-10-22 04:07:37	announced	2024-10-22: Updated project metadata.

Tank EM, Figueroa-Romero C, Hinder LM, Bedi K, Archbold HC, Li X, Weskamp K, Safren N, Paez-Colasante X, Pacut C, Thumma S, Paulsen MT, Guo K, Hur J, Ljungman M, Feldman EL, Barmada SJ, Abnormal RNA stability in amyotrophic lateral sclerosis. Nat Commun, 9(1):2845(2018) [pubmed]

curator keyword: Biological

submitter keyword: RNA, stability, amyotrophic lateral sclerosis, frontotemporal dementia, stem cells, LC-MS/MS, TMT 10plex

Sami Barmada
contact affiliation	Assistant Professor of Neurology and Angela Dobson and Lyndon Welch Professor of Neurology Department of Neurology | University of Michigan Health System 109 Zina Pitcher Place, 5015 BSRB | Ann Arbor, MI | 48109
contact email	sbarmada@umich.edu
lab head
Sami Barmada
contact affiliation	University of Michigan
contact email	sbarmada@umich.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009969
     1. Label: PRIDE project
     2. Name: RNA instability in amyotrophic lateral sclerosis