PXD017290

PXD017290 is an original dataset announced via ProteomeXchange.

Title	Comprehensive identification of full-length mRNA isoforms reveals massive diversity of neural cell-surface molecules and illuminates their function in development and disease
Description	Genes encoding cell-surface proteins are crucial for nervous system development and are implicated in neurological disorders. These genes produce alternative mRNA isoforms which remain poorly characterized, impeding our understanding of how disease-associated mutations cause pathology. Here we introduce a new strategy to reveal complete full-length isoform portfolios encoded by individual genes. Using our strategy to catalog diversity of neural cell surface molecules, we identified thousands of unannotated isoforms expressed in retina and brain. Mass spectrometry revealed that many newly-discovered proteins are expressed on the cell surface in vivo. Remarkably, we discover that the major isoform of the retinal degeneration gene CRB1 was previously overlooked. This isoform is the only one expressed by photoreceptors, the affected cells in CRB1 disease. By generating mouse mutants, we reveal a function for this isoform at the cell-cell junctions of the retinal outer limiting membrane, and we provide a causal link between loss of this Crb1 isoform and photoreceptor death. Therefore, our isoform identification strategy accelerates discovery of new gene functions relevant to disease.
HostingRepository	PRIDE
AnnounceDate	2020-08-11
AnnouncementXML	Submission_2020-08-11_04:32:42.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD017290
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Christopher Kozlowski
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Deamidated; biotinylated residue; Oxidation; Carbamidomethyl
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-27 02:26:05	ID requested
⏵ 1	2020-08-11 04:32:43	announced

Ray TA, Cochran K, Kozlowski C, Wang J, Alexander G, Cady MA, Spencer WJ, Ruzycki PA, Clark BS, Laeremans A, He MX, Wang X, Park E, Hao Y, Iannaccone A, Hu G, Fedrigo O, Skiba NP, Arshavsky VY, Kay JN, Comprehensive identification of mRNA isoforms reveals the diversity of neural cell-surface molecules with roles in retinal development and disease. Nat Commun, 11(1):3328(2020) [pubmed]

submitter keyword: Isoforms, PacBio Sequencing,Cell-surface molecules, neural development

Jeremy N. Kay
contact affiliation	Departments of 1Neurobiology and 2Ophthalmology, Duke University School of Medicine, Durham, NC, USA
contact email	jeremy.kay@duke.edu
lab head
Christopher Kozlowski
contact affiliation	Duke University
contact email	ck136@duke.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/2020/08/PXD017290

PRIDE project URI

• PRIDE
  1. PXD017290
     1. Label: PRIDE project
     2. Name: Comprehensive identification of full-length mRNA isoforms reveals massive diversity of neural cell-surface molecules and illuminates their function in development and disease