# Post-transcriptional mechanisms of gene regulation in cardiac cell growth and development

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2022 · $385,624

## Abstract

I. ABSTRACT
 Heart disease remains the leading cause of death in the United States. Despite what we know about
the risk factors associated with heart disease, the molecular mechanisms are still largely unknown. The healthy
adult heart is unique from other tissues in that the rate of protein synthesis is dramatically lower than in most
tissues and lower than the developing heart. However, during cardiac hypertrophy, translation rates increase.
This suggests a tissue-specific mechanism for regulating translation rates in the mammalian heart. Our lab has
identified a mechanism by which total protein synthesis in cardiomyocytes is decreased during development
through shortening of poly(A) tails, leading to a decrease in polysome formation through the closed-loop model
of translation. This regulation is reversed during both physiologic and pathologic hypertrophy when the
translation needs of cardiomyocytes are increased. Also, we have discovered that the nuclear poly(A) binding
protein (PABPN1) is post-transcriptionally silenced in mammalian adult cardiac and skeletal muscle but it
becomes re-expressed in pathologic cardiac hypertrophy. PABPN1 is a regulator of alternative polyadenylation
(APA) and poly(A) tail length, both of which can influence the translation of transcripts. Our central hypothesis
is that PABPN1 is dynamically regulated in cardiac myocytes to tune translation rates and suite growth needs
through a polyadenylation dependent mechanism. The objective of this proposal is to elucidate the exact
function(s) of PABPN1 in cardiac development and growth and identify how PABPN1 is regulated during these
conditions. Aims 1 and 2 will use conditional PABPN1-knockout and overexpressing mice to determine the
physiologic roles of PABPN1 in cardiac development and hypertrophy while defining the molecular basis of
PABPN1 activity and its role in determining cardiac-specific gene expression programs. In Aim 3, we will use
super-resolution microscopy, CRISPR-Cas9 mediated genome editing, and RNA antisense-oligo pulldown
approaches to identify the regulatory mechanism(s) and factors that post-transcriptionally silence PABPN1
during cardiac development.

## Key facts

- **NIH application ID:** 10418690
- **Project number:** 5R01HL126845-08
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Auinash Kalsotra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $385,624
- **Award type:** 5
- **Project period:** 2015-04-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418690

## Citation

> US National Institutes of Health, RePORTER application 10418690, Post-transcriptional mechanisms of gene regulation in cardiac cell growth and development (5R01HL126845-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10418690. Licensed CC0.

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