# Posttranscriptional Regulation of RNA Binding Proteins in Heart Failure

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $378,085

## Abstract

Summary
Heart failure is a major public heath issue worldwide and its morbidity and mortality are unacceptably high, and
remains the leading cause of morbidity, mortality, and hospitalization among adults and the elderly. Given
these clinical observations, development of new therapeutic targets is urgently required and understanding the
molecular mechanisms responsible for heart failure development and progression is critically important to
develop new therapeutic targets. For genes to produce their final functional products (proteins or non-coding
RNAs), the RNA transcripts need to be extensively processed after transcription, including splicing,
modification, transportation and translation. RNA binding proteins (RBPs) are important regulators in each step
of the complex processes of RNA metabolism and are being recognized as emerging key players in the
pathogenesis of heart failure. Although transcriptional changes have been extensively studied in the failing
hearts, very little is known about the role of posttranscriptional events in the remodeling heart. In this proposal,
we will systematically investigate the role of RNA binding protein 20 (RBM20) in the pathogenesis of heart
failure. We hypothesize that RBM20 phosphorylation and mutations on phosphorylation sites alter the
posttranscriptional process and lead to cardiac remodeling, and RBM20 isoforms and cofactors regulate fetal
gene re-expression in adult heart to promote heart failure. To test the hypothesis, we have created mutation
knock-in (KI) and double knockout mouse models to evaluate functional roles of posttranscriptional event
changes in cardiac remodeling, and determine the genes and proteins affected by the posttranscriptional
changes. KI mice will be used to evaluate the translational value with the inhibitor of nuclear transport for
RBM20-meidated nucleo-cytoplasmic trafficking. Two specific aims are proposed in this proposal. 1) Determine
the functional roles of RBM20 phosphorylation and genetic mutations on phosphorylation sites in the
pathogenesis of heart failure; 2) Determine the molecular/cellular mechanisms of RBM20 mediated
posttranscriptional regulation of heart failure through cofactors and RBM20 isoforms. The achievement of the
proposed aims will gain new information regarding RBPs-mediated posttranscriptional regulation in the
pathogenesis of heart failure and provide a new paradigm for the mechanistic study on genetic mutations-
induced heart failure.

## Key facts

- **NIH application ID:** 10469455
- **Project number:** 5R01HL148733-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Wei Guo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $378,085
- **Award type:** 5
- **Project period:** 2020-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469455

## Citation

> US National Institutes of Health, RePORTER application 10469455, Posttranscriptional Regulation of RNA Binding Proteins in Heart Failure (5R01HL148733-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10469455. Licensed CC0.

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