PXD008260

PXD008260 is an original dataset announced via ProteomeXchange.

Title	A U1-70K Protein Interaction Network Reveals a Functional Class of RNA Binding Proteins with Mixed Charge Domains
Description	U1 small nuclear ribonucleoprotein 70 kDa (U1-70K) and other proteins of the spliceosome complex are mislocalized to cytoplasmic aggregates in Alzheimer’s disease (AD) brain, yet understanding of the specific mechanisms that cause their aggregation is limited. Many of the RNA binding proteins (RBPs) that aggregate in neurodegenerative diseases, including TDP-43 and FUS, self-assemble into RNA granules through disordered low complexity (LC) domains. We report here that a LC domain within U1-70K, that is comprised of tandem arrays of basic (R/K) and acidic (D/E) residues, shares many of the same properties of the Q/N-rich prion-like LC domains found in TDP-43 and FUS. These properties include the ability to self-assemble into oligomers, and to form nuclear granules in cells. To analyze the functional roles of the U1-70K LC domains, we performed co-immunoprecipitation of recombinant U1-70K and deletions lacking the C-terminal LC domain(s) followed by quantitative proteomics. Using a network-driven approach, functional classes of U1-70K interacting proteins were identified that showed a varying dependency on the U1-70K LC domain(s) for their interaction. We characterize a family of structurally homologous RBPs containing U1-70K LC1-like domains including LUC7L3 and RBM25, which require their respective LC1-like domains for reciprocal interactions with U1-70K and for participation in nuclear RNA granules. Finally, we also show that the LC1 domain of U1-70K can interact with Tau from AD brain supporting a hypothesis that mixed charge structural motifs on U1-70K and other RBPs could mediate cooperative interactions with pathological tau isoforms
HostingRepository	PRIDE
AnnounceDate	2018-06-21
AnnouncementXML	Submission_2018-06-21_07:57:16.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eric Dammer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-11-22 01:15:58	ID requested
⏵ 1	2018-06-21 07:57:17	announced

Bishof I, Dammer EB, Duong DM, Kundinger SR, Gearing M, Lah JJ, Levey AI, Seyfried NT, RNA-binding proteins with basic-acidic dipeptide (BAD) domains self-assemble and aggregate in Alzheimer's disease. J Biol Chem, 293(28):11047-11066(2018) [pubmed]

curator keyword: Biological

submitter keyword: U1-70K

Nicholas T. Seyfried
contact affiliation	Emory University School of Medicine Departments of Biochemistry, Neurology
contact email	nseyfri@emory.edu
lab head
Eric Dammer
contact affiliation	Emory University
contact email	edammer@emory.edu
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/2018/06/PXD008260

PRIDE project URI

• PRIDE
  1. PXD008260
     1. Label: PRIDE project
     2. Name: A U1-70K Protein Interaction Network Reveals a Functional Class of RNA Binding Proteins with Mixed Charge Domains