PXD001668

PXD001668 is an original dataset announced via ProteomeXchange.

Title	Proteomic analyses reveal that loss of TDP-43 affects RNA processing and intracellular transport
Description	Transactive response DNA-binding protein 43 (TDP-43) is a predominantly nuclear, ubiquitously expressed RNA and DNA-binding protein. It recognises and binds to UG repeats and is involved in pre-mRNA splicing, mRNA stability and microRNA metabolism. TDP-43 is essential in early embryonic development but accumulates in cytoplasmic aggregates in amyotrophic lateral sclerosis (ALS) and tau-negative frontotemporal lobar degeneration (FTLD). It is not known yet whether cytoplasmic aggregates of TDP-43 are toxic or protective but they are often associated with a loss of TDP-43 from the nucleus and neurodegeneration may be caused by a loss of normal TDP-43 function or a gain of toxic function. Here we present a proteomic study to analyse the effect of loss of TDP-43 on the proteome. Our results indicate that TDP-43 is an important regulator of RNA metabolism and intracellular transport. We show that Ran-binding protein 1 (RanBP1), DNA methyltransferase 3 alpha (Dnmt3a) and chromogranin B (CgB) are downregulated upon TDP-43 knockdown. Subsequently, transportin 1 level is increased as a result of RanBP1 depletion. Improper regulation of these proteins and the subsequent disruption of cellular processes may play a role in the pathogenesis of the TDP-43 proteinopathies ALS and FTLD.
HostingRepository	PRIDE
AnnounceDate	2015-06-29
AnnouncementXML	Submission_2015-06-29_08:04:10.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD001668
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Xiaoke Yin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2015-01-13 02:02:16	ID requested
⏵ 1	2015-06-29 08:04:11	announced

Š, talekar M, Yin X, Rebolj K, Darovic S, Troakes C, Mayr M, Shaw CE, Rogelj B, Proteomic analyses reveal that loss of TDP-43 affects RNA processing and intracellular transport. Neuroscience, 293():157-70(2015) [pubmed]

curator keyword: Biomedical

submitter keyword: TDP-43, RanBP1, amyotrophic lateral sclerosis, frontotemporal lobar degeneration, comparative proteomics, intracellular transport

Manuel Mayr
contact affiliation	King's British Heart Foundation Centre, King's College London, UK
contact email	manuel.mayr@kcl.ac.uk
lab head
Xiaoke Yin
contact affiliation	Cardiovascular Division, King's College London
contact email	xiaoke.yin@kcl.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001668
     1. Label: PRIDE project
     2. Name: Proteomic analyses reveal that loss of TDP-43 affects RNA processing and intracellular transport