# Post-transcriptional regulation by the YBX3 RNA-binding protein in skeletal muscle

> **NIH NIH R15** · HAVERFORD COLLEGE · 2022 · $421,197

## Abstract

PROJECT SUMMARY/ABSTRACT
Post-transcriptional control permeates biology from proliferation to development. RNA-binding proteins (RBPs)
dictate which messenger (m)RNAs are regulated, and how, where, and when that regulation occurs. Their roles
in biology are incontrovertible, and emphasized by RBP dysfunctions that cause disease, including cancer,
obesity and muscular atrophies. The long-term goal is to understand how RNA-protein complexes dictate and
respond to complex biological events to realize how defects in these complexes result in disease. The objective
of this proposal is to understand the diverse post-transcriptional regulation of the RBP YBX3, and connect its
regulation to key biological processes and disease. The central hypothesis, which was formulated based on
previous findings and preliminary data, is that YBX3 post-transcriptionally regulates mRNAs via multiple
mechanisms, and this control is required to maintain amino acid transport in skeletal muscle. A multi-disciplinary
approach that combines biochemistry, “omics”, bioinformatics and mammalian cell culture to dissect how YBX3
regulates via diverse mechanisms, and the role for its post-transcriptional control of amino acid transporters in
skeletal muscles. The rationale for the proposed work is that once the diverse post-transcriptional control
mechanisms are understood, this can be used as a paradigm for other clinically relevant RBPs, and to potentially
develop therapeutic strategies based on this regulation. The objective of this project will be accomplished by
three specific aims: 1) Define how the modular domains of YBX3 contribute to post-transcriptional regulation.
The working hypothesis is that the modular domains of YBX3 help determine the diverse regulatory outcomes.
The investigators will modify a well-established biochemical assay to assay the regulatory contribution of each
domain. 2) Identify YBX3-dependent complexes formed on specific mRNAs. The working hypothesis is that
different complexes form on mRNAs that YBX3 either activates or represses. RNA pull-down approaches will be
used to identify transcript specific complexes using targeted and non-targeted methods. 3) Characterize the role
of YBX3's post-transcriptional control of amino acid transport in skeletal muscle. The working hypothesis is that
YBX3 stabilizes transporter mRNAs to maintain amino acid homeostasis in skeletal muscle that is critical for
differentiation in this tissue. Amino acid mRNA stability, the intracellular levels of amino acids and differentiation
will be assessed when YBX3 is depleted in skeletal muscle cells. This proposal is innovative because it 1)
establishes how a single RBP controls mRNAs via multiple mechanisms, which can be used as a paradigm for
other multi-regulatory RBPs, and 2) defines how post-transcriptional regulation impacts amino acid transport in
skeletal muscle that could lead to new therapeutic strategies of a process that is impaired with aging. The
proposed work is...

## Key facts

- **NIH application ID:** 10439013
- **Project number:** 1R15GM146205-01
- **Recipient organization:** HAVERFORD COLLEGE
- **Principal Investigator:** Amy M. Cooke
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $421,197
- **Award type:** 1
- **Project period:** 2022-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439013

## Citation

> US National Institutes of Health, RePORTER application 10439013, Post-transcriptional regulation by the YBX3 RNA-binding protein in skeletal muscle (1R15GM146205-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10439013. Licensed CC0.

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