Poster abstracts
Poster number 121 submitted by Sandip Chorghade
Posttranscriptional Silencing of Poly A Binding Nuclear Protein 1 (PABPN1) in Cardiomyocytes Regulates Heart Development and Disease Progression
Sandip Chorghade, Subhashis Natua,Joe Seimetz,Chaitali Misra (Department of Biochemistry ,University of Illinois Urbana-Champaign), Xander Wehrens (Department of Molecular Physiology and Biophysics, Baylor College of Medicine), Jiwang Chen (Department of Medicine, University of Illinois Chicago), Auinash Kalsotra (Department of Biochemistry, and Carl R.Woese Institute for Genomic Biology,University of Illinois Urbana-Champaign)
Abstract:
The nuclear poly(A) binding protein (PABPN1) is a highly conserved protein with ubiquitous expression, pivotal in 3’-poly(A) tail elongation and alternative polyadenylation (ApA). We elucidate the post-transcriptional silencing of PABPN1 during postnatal heart development, contrasting with its re-expression in heart failure. Our investigations reveal that in healthy cardiomyocytes, PABPN1 silencing is mediated by the retention of its incompletely spliced mRNA within nuclear speckles. Intriguingly, in cardiomyopathy, stored PABPN1 mRNA undergoes splicing and translation. we demonstrate that sustained PABPN1 expression in cardiomyocytes induces significant structural and functional abnormalities in heart leading to failure. These abnormalities arise from the over-expression of cardiac transcripts due to shortened 3’UTRs and increased poly(A) tail lengths. Our findings underscore the critical role of developmental PABPN1 silencing, regulated by mRNA splicing and localization, in maintaining heart function, while its continual expression drives cardiomyopathy in the adult heart.
Keywords: PABPN1, ApA, Intron retaintion