Stage-specific requirement for METTL3-dependent m⁶A epitranscriptomic regulation during myogenesis

Area of Science:

• Molecular Biology
• Epigenetics
• Skeletal Muscle Physiology

Background:

• The role of N⁶-methyladenosine (m⁶A) modification in skeletal muscle myogenesis and homeostasis is not well understood.
• The specific function of methyltransferase-like 3 (METTL3) in regulating muscle cell development requires further investigation.

Purpose of the Study:

• To investigate the role of METTL3-mediated m⁶A modification in skeletal muscle myogenesis.
• To elucidate the mechanisms by which METTL3 regulates myoblast fusion and muscle regeneration.

Main Methods:

• Systematic analysis of m⁶A epitranscriptomic changes during myogenesis.
• High-resolution m⁶A mapping to identify METTL3-regulated m⁶A sites.
• Analysis of Mettl3 expression and transcriptomic alterations post-injury.
• Identification and validation of direct targets of METTL3.

Main Results:

• METTL3-mediated m⁶A modifications are essential for myoblast fusion in both differentiation and regeneration.
• Mettl3 expression is significantly induced after muscle injury, correlating with transcriptomic shifts.
• Distinct dynamic patterns of METTL3-regulated m⁶As were observed during differentiation.
• Myogenic fusion factors Mymx and Mymk were identified as direct targets of METTL3.

Conclusions:

• METTL3 acts as a critical regulator of myoblast fusion dynamics.
• METTL3-mediated m⁶A modification plays a vital role in myogenic programming and skeletal muscle regeneration.
• This study provides valuable multi-omics data on METTL3's function in muscle biology.