# Microtubule-mediated tRNA localization in cardiac homeostasis and hypertrophy

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2024 · $74,284

## Abstract

PROJECT SUMMARY
In response to hemodynamic demands faced by the heart, cardiomyocytes adapt and remodel primarily through
changes in myocyte thickness or length. In conditions like cardiovascular exercise, changes in physiological
hypertrophy can aid in improving cardiac function. However, in conditions of prolonged elevated blood pressure,
heart rate, and excessive weight gain, pathological hypertrophy occurs and ultimately can contribute to heart
failure. Changes in cardiomyocyte growth and atrophy that subsequently impact physiological and pathological
cardiac remodeling are dictated by changes in protein synthesis. And while there is significant progress in
understanding the transcriptional and translational changes that mediate maladaptive cardiac remodeling, little
is known about the changes in the most abundant noncoding RNAs that link these two processes: transfer RNAs
(tRNA). Outside of the notion that Polymerase III activity, which is required for tRNA transcription, increases in
response to cardiac pressure overload, almost completely nothing is known about how alterations in tRNA
transcription, transport, and localization impact sites of protein synthesis and, ultimately, cardiac remodeling.
Considering that heart failure and the preceding changes in myocyte size contribute to the majority of deaths in
the United States, there is an unmet need for new therapies that target malignant protein synthesis in pathological
cardiac hypertrophy. Hence, this need may be met by identifying new regulating transcription and translational
control from a novel tRNA-centric view. In this proposal, we will examine the relationship between tRNA
transcription, transport, and localization in cardiac homeostasis and hypertrophy. We have identified that tRNAs,
which are believed to primarily rely on passive diffusion for appropriate localization, require the microtubule
network for proper localization in the heart. We hypothesize that pathological and physiological hypertrophy
induce different changes in tRNA transcription; but that both types of growth require motor protein-mediated
active transport of tRNAs along the microtubule network to facilitate necessary increases in protein synthesis for
cardiomyocyte growth. We will test our hypothesis by carrying out the following aims: (1) To determine the role
of microtubules in tRNA trafficking and localization in the cardiomyocyte. (2) To characterize the localization and
expression of mammalian tRNAs during cardiac remodeling. (3) To identify the proteins that facilitate tRNA
trafficking in cardiomyocytes. This work will be carried out in the laboratory of Dr. Benjamin Prosser, an expert
on microtubules, cardiomyocyte mRNA trafficking, and cardiac remodeling. Successful completion of this work
will have the positive impact of defining how changes in tRNA transcription, localization, and trafficking impact
cardiac homeostasis and hypertrophy and thus result in the potential new strategies that target heart f...

## Key facts

- **NIH application ID:** 10999392
- **Project number:** 5F32HL170583-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Jennifer Morgan Petrosino
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,284
- **Award type:** 5
- **Project period:** 2023-08-07 → 2025-08-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10999392

## Citation

> US National Institutes of Health, RePORTER application 10999392, Microtubule-mediated tRNA localization in cardiac homeostasis and hypertrophy (5F32HL170583-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10999392. Licensed CC0.

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