PXD015278

PXD015278 is an original dataset announced via ProteomeXchange.

Title	Identification of SART3 as a pre-miR-34a–binding protein
Description	MicroRNAs (miRNAs or miRs) are small, noncoding RNAs that are implicated in the regulation of nearly all biological processes. Global miRNA biogenesis is altered in many cancers and RNA-binding proteins (RBPs) have been shown to play a role in this process, presenting a promising avenue for targeting miRNA dysregulation in disease. miR-34a exhibits tumor-suppressive functions by targeting cell cycle regulators CDK4/6 and anti-apoptotic factor Bcl-2, among other regulatory pathways such as Wnt, TGF-, and Notch signaling. Many cancers show downregulation or loss of miR-34a, and synthetic miR-34a supplementation has been shown to inhibit tumor growth in vivo; however, the post-transcriptional mechanisms by which miR-34a is lost in cancer are not entirely understood. Here, we have used a proteomics-mediated approach to identify Squamous cell carcinoma antigen recognized by T-cells 3 (SART3) as a putative pre-miR-34a-binding protein. SART3 is a spliceosome recycling factor and nuclear RBP with no previously reported role in miRNA regulation. We demonstrate that SART3 binds pre-miR-34a with specificity over pre-let-7d and begin to elucidate a new functional role for this protein in non-small lung cancer cells. Overexpression of SART3 led to increased miR-34a levels, downregulation of the miR-34a target genes CDK4 and CDK6, and cell cycle arrest in the G1 phase. In vitro binding studies showed that the RNA-recognition motifs within the SART3 sequence are responsible for selective pre-miR-34a binding. Collectively, our results present evidence for an influential role of SART3 in miR-34a biogenesis and cell cycle progression.
HostingRepository	PRIDE
AnnounceDate	2019-10-14
AnnouncementXML	Submission_2019-10-25_04:09:51.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dylan Mitchell
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-02 01:19:38	ID requested
1	2019-10-14 01:21:01	announced
⏵ 2	2019-10-25 04:09:53	announced	2019-10-25: Updated publication reference for PubMed record(s): 31619517.

Sherman EJ, Mitchell DC, Garner AL, cell cycle arrest in lung cancer cells. J Biol Chem, 294(46):17188-17196(2019) [pubmed]

submitter keyword: SART3, miRNA, miR34, proteomics, RBPs

Amanda Lee Garner
contact affiliation	Department of Medicinal Chemistry, University of Michigan
contact email	algarner@umich.edu
lab head
Dylan Mitchell
contact affiliation	University of Michigan
contact email	dylancm@umich.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/2019/10/PXD015278

PRIDE project URI

• PRIDE
  1. PXD015278
     1. Label: PRIDE project
     2. Name: Identification of SART3 as a pre-miR-34a–binding protein