Platr4 is an early embryonic lncRNA that exerts its function downstream on cardiogenic mesodermal lineage commitment

Hazra, Rasmani, Brine, Lily, Garcia, Libia, Benz, Brian, Chirathivat, Napon, Shen, Michael M, Wilkinson, John Erby, Lyons, Scott K, Spector, David L (November 2022) Platr4 is an early embryonic lncRNA that exerts its function downstream on cardiogenic mesodermal lineage commitment. Developmental Cell, 57 (21). 2450-2468.e7. ISSN 1534-5807

URL: https://www.ncbi.nlm.nih.gov/pubmed/36347239

DOI: 10.1016/j.devcel.2022.10.002

Abstract

The mammalian genome encodes thousands of long non-coding RNAs (lncRNAs), many of which are developmentally regulated and differentially expressed across tissues, suggesting their potential roles in cellular differentiation. Despite this expression pattern, little is known about how lncRNAs influence lineage commitment at the molecular level. Here, we demonstrate that perturbation of an embryonic stem cell/early embryonic lncRNA, pluripotency-associated transcript 4 (Platr4), directly influences the specification of cardiac-mesoderm-lineage differentiation. We show that Platr4 acts as a molecular scaffold or chaperone interacting with the Hippo-signaling pathway molecules Yap and Tead4 to regulate the expression of a downstream target gene, Ctgf, which is crucial to the cardiac-lineage program. Importantly, Platr4 knockout mice exhibit myocardial atrophy and valve mucinous degeneration, which are both associated with reduced cardiac output and sudden heart failure. Together, our findings provide evidence that Platr4 is required in cardiac-lineage specification and adult heart function in mice.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell differentiation organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > chaperones organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > differentiation organs, tissues, organelles, cell types and functions > tissues types and functions > endoderm organism description > animal > mammal organs, tissues, organelles, cell types and functions > tissues types and functions > endoderm > mesoderm organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > pluripotency bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organism description > animal > mammal > rodent organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > tissues types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:	Brine, Lily D Garcia, Libia Lyons, Scott Spector, David L. Hazra, Rasmani
Communities:	CSHL labs > Lyons lab CSHL labs > Spector lab CSHL Cancer Center Program CSHL Cancer Center Program > Gene Regulation and Inheritance Program CSHL Cancer Center Shared Resources > Animal Services CSHL Cancer Center Shared Resources > Flow Cytometry Service CSHL Cancer Center Shared Resources > Histology Service CSHL Cancer Center Shared Resources > Microscopy Service CSHL Cancer Center Shared Resources > Next Generation Sequencing Service
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	7 November 2022
Date Deposited:	28 Nov 2022 16:19
Last Modified:	09 Feb 2024 18:53
PMCID:	PMC9680017
URI:	https://repository.cshl.edu/id/eprint/40762

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