ArticleNucleic acids research2022
Definition of germ layer cell lineage alternative splicing programs reveals a critical role for Quaking in specifying cardiac cell fate.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Review
- Competition for the conserved branch point sequence influences physiological outcomes in pre-mRNA splicing.eLife · 2026Article
- A machine learning classifier to identify and prioritise genes associated with murine cardiac development.PLoS genetics · 2026Article
- CisBP-RNA: a web resource for eukaryotic RNA-binding proteins and their motifs.Nucleic acids research · 2026Article
- QKI ensures splicing fidelity during cardiogenesis by engaging the U6 tri-snRNP to activate splicing at weak 5' splice sites.bioRxiv : the preprint server for biology · 2025Article
- Amniotic Fluid Reduces Liver Fibrosis By Attenuating Hepatic Stellate Cell Activation.bioRxiv : the preprint server for biology · 2025Article
- LincRNA-ASAO promotes dental pulp repair through interacting with PTBP1 to increase ALPL alternative splicing.Stem cell research & therapy · 2025Article
- Integrated multi-omics analysis identifies features that predict human pluripotent stem cell-derived progenitor differentiation to cardiomyocytes.Journal of molecular and cellular cardiology · 2024Article
- RNA-binding proteins in cardiovascular biology and disease: the beat goes on.Nature reviews. Cardiology · 2024Review
- Quaking regulates circular RNA production in cardiomyocytes.Journal of cell science · 2023Article
- The RNA-binding protein QKI governs a muscle-specific alternative splicing program that shapes the contractile function of cardiomyocytes.Cardiovascular research · 2023Article
- The emerging significance of splicing in vertebrate development.Development (Cambridge, England) · 2022Review
- Article
- The Emerging Roles of the RNA Binding Protein QKI in Cardiovascular Development and Function.Frontiers in cell and developmental biology · 2021Review
- Genome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq Data.Frontiers in genetics · 2021Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Alternative splicing is critical for development; however, its role in the specification of the three embryonic germ layers is poorly understood. By performing RNA-Seq on human embryonic stem cells (hESCs) and derived definitive endoderm, cardiac mesoderm, and ectoderm cell lineages, we detect distinct alternative splicing programs associated with each lineage. The most prominent splicing program differences are observed between definitive endoderm and cardiac mesoderm. Integrative multi-omics analyses link each program with lineage-enriched RNA binding protein regulators, and further suggest a widespread role for Quaking (QKI) in the specification of cardiac mesoderm. Remarkably, knockout of QKI disrupts the cardiac mesoderm-associated alternative splicing program and formation of myocytes. These changes arise in part through reduced expression of BIN1 splice variants linked to cardiac development. Mechanistically, we find that QKI represses inclusion of exon 7 in BIN1 pre-mRNA via an exonic ACUAA motif, and this is concomitant with intron removal and cleavage from chromatin. Collectively, our results uncover alternative splicing programs associated with the three germ lineages and demonstrate an important role for QKI in the formation of cardiac mesoderm.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.