PXD016186

PXD016186 is an original dataset announced via ProteomeXchange.

Title	The long noncoding RNA Caren protects against heart failure via suppressing the Hint1-ATM signaling pathway
Description	Long noncoding RNAs (lncRNAs) have potential as novel therapeutic targets in cardiac disease, but their function in heart failure (HF) is not yet fully understood. Using a gene trapping approach in mouse embryonic stem cells, we identified a novel cytoplasmic lncRNA, dubbed Caren (cardiomyocyte-enriched noncoding transcript), which was predominantly expressed in cardiomyocytes. Caren was markedly downregulated in the mouse failing heart that was subjected to transverse aortic constriction (TAC). The ablation of Caren in the mouse heart accelerated HF-related phenotypes by TAC, whereas mice overexpressing Caren (CAG-Caren Tg mice) resisted TAC-induced HF. Proteomic analysis identified histidine triad nucleotide-binding protein 1 (Hint1) as a Caren target protein, while bioinformatic analysis of proteome revealed that Caren regulates the proteins involved in mitochondrial energetics in the heart. Furthermore, we found that Caren suppressed Hint1 expression at the translational level and that Hint1 overexpression reduced mitochondrial respiration capacity. Similar to CAG-Caren Tg mice, the reduced Hint1 expression in mice exerted cardioprotective effects on TAC-induced HF, which was associated with the decreased level of ATM serine/threonine kinase phosphorylation, known to activate DNA damage responses. Overall, we identify a novel cytoplasmic lncRNA that protects against the development of HF through suppressing the Hint1-ATM signaling, which presumably maintains mitochondrial energetics and prevents the DNA damage under pathological stress.
HostingRepository	PRIDE
AnnounceDate	2021-02-08
AnnouncementXML	Submission_2021-02-08_10:56:01.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anna Bakhtina
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-07 02:10:50	ID requested
⏵ 1	2021-02-08 10:56:01	announced

Dataset with its publication pending

submitter keyword: Mouse, heart failure, lncRNA

Sarah Franklin
contact affiliation	Department of Internal Medicine - Cardiology Division Nora Eccles Harrison Cardiovascular Research and Training Institute, Univeristy of Utah, Salt Lake City, UT, USA
contact email	sarah.franklin@utah.edu
lab head
Anna Bakhtina
contact affiliation	University of Utah
contact email	anna.bakhtina91@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD016186
     1. Label: PRIDE project
     2. Name: The long noncoding RNA Caren protects against heart failure via suppressing the Hint1-ATM signaling pathway