Transcription Factor GATA4 Regulates Cell Type-Specific Splicing Through Direct Interaction With RNA in Human Induced Pluripotent Stem Cell-Derived Cardiac Progenitors.
Lili ZhuKrishna ChoudharyBarbara Gonzalez-TeranYen-Sin AngReuben ThomasNicole R StoneLei LiuPing ZhouChenchen ZhuHongmei RuanYu HuangShibo JinAngelo PeloneroFrances KobackArun PadmanabhanNandhini SadagopanAustin HsuMauro W CostaCasey A GiffordJoke G van BemmelRuth HüttenhainVasanth VedanthamBruce R ConklinBrian L BlackBenoit G BruneauLars SteinmetzNevan J KroganKatherine S PollardDeepak SrivastavaPublished in: Circulation (2022)
This study shows that in addition to its well described transcriptional function, GATA4 interacts with members of the spliceosome complex and regulates cell type-specific alternative splicing via sequence-specific interactions with RNA. Several genes that have splicing regulated by GATA4 have functional consequences and many are associated with dilated cardiomyopathy, suggesting a novel role for GATA4 in achieving the necessary cardiac proteome in normal and stress-responsive conditions.