Characterization of Long Non-coding RNAs Modified by m⁶A RNA Methylation in Skeletal Myogenesis

Area of Science:

• Molecular Biology
• Epigenetics
• Developmental Biology

Background:

• Skeletal muscle development requires precise gene regulation by both mRNA and long non-coding RNAs (lncRNAs).
• N⁶-methyladenosine (m⁶A) is a crucial epitranscriptomic modification involved in various biological processes.
• The role and patterns of m⁶A modification in lncRNAs during muscle development remain largely unexplored.

Purpose of the Study:

• To profile transcriptome-wide m⁶A methylation patterns in lncRNAs during mammalian skeletal muscle development.
• To investigate the relationship between m⁶A modification, lncRNA expression, and the methyltransferase METTL3 in developing muscle.
• To explore the potential functional correlation between m⁶A-modified lncRNAs and their neighboring mRNAs.

Main Methods:

• RNA sequencing (RNA-seq) to identify differentially expressed lncRNAs.
• Methylated RNA immunoprecipitation (MeRIP) sequencing to map m⁶A modifications on lncRNAs.
• Analysis of m⁶A motif (DRACH) presence and correlation with transcript abundance.

Main Results:

• Identification of numerous temporally differentially expressed lncRNAs in developing mouse myoblasts and myotubes.
• Detection of the consensus m⁶A motif (DRACH) within m⁶A-modified lncRNAs.
• Positive correlation observed between m⁶A methylation levels and transcript abundance of lncRNAs.
• Demonstration that METTL3 influences the expression levels of these m⁶A-modified lncRNAs.

Conclusions:

• This study provides a foundational understanding of m⁶A-mediated epitranscriptomic regulation in lncRNAs during muscle development.
• m⁶A modification patterns in lncRNAs are temporally dynamic and influenced by METTL3.
• The findings suggest a potential functional link between m⁶A-modified lncRNAs and the regulation of nearby mRNAs in developing skeletal muscle.