The m6A reader IGF2BP3 facilitates myogenesis by activating the CAMK2B-MEF2C axis

Area of Science:

• Epigenetics
• Molecular Biology
• Animal Science

Background:

• Skeletal muscle development is crucial for livestock meat quality and productivity.
• N6-methyladenosine (m6A) RNA methylation regulates myogenesis, but the role of m6A reader protein IGF2BP3 in goats is unknown.

Purpose of the Study:

• To investigate the function of IGF2BP3 and its m6A-mediated regulation in goat skeletal muscle development.
• To identify molecular mechanisms underlying IGF2BP3's role in myogenesis.

Main Methods:

• Analysis of IGF2BP3 expression in goat longissimus muscles at different developmental stages and during in vitro myogenesis.
• Loss-of-function experiments to assess the impact of IGF2BP3 depletion on myoblast proliferation and differentiation.
• RNA-sequencing, RIP-qPCR, and mRNA stability assays to identify target genes and regulatory pathways.

Main Results:

• IGF2BP3 expression varies with developmental stage and increases during myogenic differentiation.
• IGF2BP3 depletion significantly impairs myoblast proliferation and differentiation.
• IGF2BP3 binds to m6A-modified CAMK2B and MEF2C mRNAs, stabilizing them and activating the CAMK2B-MEF2C axis crucial for myogenesis.

Conclusions:

• IGF2BP3 is a key regulator of goat myogenesis through an m6A-dependent mechanism.
• The identified IGF2BP3-CAMK2B-MEF2C pathway offers novel insights into epigenetic control of muscle development.
• Findings provide targets for precision breeding to enhance goat meat production by optimizing muscle traits.