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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #435431
Research Project: Regulatory Aspects of Obesity Development

Location: Children's Nutrition Research Center

Title: 3'UTR mapping reveals alternative polyadenylation in right ventricular failure

Author
item NEUPANE, RAHUL - Houston Methodist Research Institute
item NATARAJAN, KARTIGA - Houston Methodist Research Institute
item SUAREZ, ERIC - Houston Methodist Research Institute
item POWNALL, HENRY - Houston Methodist Research Institute
item HUANG, KAI-LIEH - University Of Rochester
item WAGNER, ERIC - University Of Rochester
item VERMA, AJAY - Baylor College Of Medicine
item MAJJI, RAMBABU - Baylor College Of Medicine
item YALAMANCHILI, HARI - Children'S Nutrition Research Center (CNRC)
item GUHA, ASHRITH - Houston Methodist Research Institute
item THANDAVARAYAN, RAJARAJAN - Houston Methodist Research Institute

Submitted to: Circulation Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/31/2026
Publication Date: 2/25/2026
Citation: Neupane, R., Natarajan, K., Suarez, E.E., Pownall, H.J., Huang, K., Wagner, E.J., Verma, A.K., Majji, R., Yalamanchili, H.K., Guha, A., Thandavarayan, R.A. 2026. 3'UTR mapping reveals alternative polyadenylation in right ventricular failure. Circulation Research. 138(7). Article e327629. https://doi.org/10.1161/CIRCRESAHA.125.327629.
DOI: https://doi.org/10.1161/CIRCRESAHA.125.327629

Interpretive Summary: Heart disease is one of the leading causes of death in the United States, and poor diet, obesity, and metabolic conditions like diabetes are among its biggest drivers. The right side of the heart is responsible for pumping blood to the lungs, and when it fails, the consequences are serious, survival outcomes are poor, and treatment options remain very limited. Think of the genetic messages inside our cells like instruction manuals for making proteins. Those manuals must be read, edited, and finished correctly for the right proteins to be made in the right amounts. What we found in failing right heart tissue is that the finishing step, where the ends of those instruction manuals are sealed, was going wrong in more than 500 genes at once. The affected genes were concentrated in pathways that drive tissue scarring and cardiac stress, suggesting this is not a random error but an active part of how the disease progresses. When the ends of gene messages are cut too short, the proteins that get made can behave differently, and the normal safeguards on harmful processes can be lost. Understanding which genes are affected and how their messages are being altered opens the door to identifying new targets for heart failure treatment. Because heart disease risk is so tightly tied to diet, body weight, and metabolic health, findings like these bring us closer to understanding the molecular path from poor nutrition to a failing heart, and where along that path we might one day intervene.

Technical Abstract: Global PAC-seq profiling revealed extensive 3'UTR remodeling in right ventricular (RV) failure, dominated by 3'UTR shortening across hundreds of transcripts enriched for TGF-ß signaling, myogenesis, and oxidative phosphorylation. Comparison with left ventricular APA maps demonstrated minimal overlap, confirming RV-specific APA remodeling. Integration with transcriptomic data across RV disease stages revealed APA activation occurring specifically during decompensation. CPSF6, a core distal polyadenylation site regulator, was identified as significantly reduced in failing RV tissue, with this loss restricted to the RV while left ventricular expression remained preserved, pointing to a chamber-specific and disease-stage-specific mechanism of APA dysregulation in cardiac failure.