# m6A mRNA modifications and myogenesis

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2020 · $169,400

## Abstract

Project Summary
N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic mRNA and long noncoding
RNAs. m6A is induced by the Mettl3 complex most commonly near stop codons and 3’ UTRs in mRNAs. m6A
recruits the YTH domain family of m6A-binding proteins, which then control almost every aspect of RNA
metabolism, including alternative splicing, nuclear export, stability, and translation. Several thousand mRNA
regions are modified by m6A in a given cell population, primarily at the consensus sequence of DRACH (D=A,
G, or U; R=A or G; H=A, C, or U). Reflecting the diverse molecular functions of m6A, it also regulates a wide
range of biological phenomena, such as cancer cell proliferation, neural development, and pluripotent stem cell
differentiation. However, the roles of m6A in muscle cell differentiation remain largely elusive. The PI’s group
recently found that one of the Fkbp family member of peptidyl prolyl isomerases interacts with the Mettl3 complex.
In addition, depletion of the Fkbp inhibited myoblast differentiation and decreased the total level of m6A in the
cells, both of which were recapitulated by Mettl3 depletion. At a molecular level, the Fkbp promotes cis-trans
isomerization of Mettl3 and its related protein Mettl14 in vitro. Based on these findings, they hypothesized that
the Fkbp regulates the m6A level of myoblast mRNAs through isomerization of Mettl3 and Mettl14. Three aims
were proposed to investigate this hypothesis. Aim 1 will determine genome-wide distribution of m6A in myoblasts
at a single nucleotide level and study how the pattern changes by depletion of the Fkbp. Aim 2 will characterize
how m6A affects metabolism of several most abundantly modified myoblast-specific mRNAs. Aim 3 will study
how Fkbp8 regulates Mettl3 and Mettl14, focusing on phosphorylation and isomerization of the proteins. These
studies are expected to lay a solid foundation for a future study of the roles of m6A in muscle cells.

## Key facts

- **NIH application ID:** 10013127
- **Project number:** 5R21AR076167-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Nobuaki Kikyo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $169,400
- **Award type:** 5
- **Project period:** 2019-09-09 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013127

## Citation

> US National Institutes of Health, RePORTER application 10013127, m6A mRNA modifications and myogenesis (5R21AR076167-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10013127. Licensed CC0.

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