Natural antisense RNA Foxk1‑AS promotes myogenic differentiation by inhibiting Foxk1 activity

Cell Communication and Signaling, 2022 · DOI: https://doi.org/10.1186/s12964-022-00896-2 · Published: April 30, 2022

Simple Explanation

This study identifies a novel natural antisense RNA called Foxk1-AS, which is transcribed from the opposite strand of the Foxk1 gene. It is shown to play a role in muscle development. The researchers found that Foxk1-AS can decrease the expression of Foxk1, a gene that inhibits muscle differentiation. By reducing Foxk1 levels, Foxk1-AS promotes the differentiation of myoblasts (muscle precursor cells) and the regeneration of damaged muscle fibers. Further investigation revealed that Foxk1-AS influences the activity of Mef2c, a transcription factor crucial for muscle gene expression. Foxk1-AS essentially 'rescues' Mef2c activity by suppressing Foxk1, ultimately leading to enhanced muscle differentiation and regeneration.

Study Duration

Not specified

Participants

C2C12 cells, C57BL6 male wild-type (WT) mice

Evidence Level

In vitro and in vivo study

Key Findings

1
Foxk1-AS is a natural antisense RNA transcribed from the opposite strand of the Foxk1 gene and is completely incorporated in the 3′ UTR of Foxk1.
2
Overexpression of Foxk1-AS inhibits Foxk1 expression in C2C12 cells and tibialis anterior muscle tissue, promoting myoblast differentiation and regeneration of damaged muscle fibers.
3
Foxk1-AS promotes Mef2c activity by repressing Foxk1 expression, thereby promoting myogenic differentiation and regeneration of damaged muscle fibers.

Research Summary

This study identifies and characterizes a novel natural antisense RNA, Foxk1-AS, which is transcribed from the opposite strand of the Foxk1 gene. Foxk1-AS is found to be located within the 3' UTR of Foxk1. The study demonstrates that Foxk1-AS negatively regulates Foxk1 expression both in vitro (C2C12 cells) and in vivo (tibialis anterior muscle tissue), leading to enhanced myoblast differentiation and regeneration of damaged muscle fibers. Mechanistically, Foxk1-AS promotes the activity of Mef2c, a key transcription factor for muscle gene expression, by repressing Foxk1, which normally inhibits Mef2c. This ultimately results in improved muscle differentiation and regeneration.

Practical Implications

Therapeutic Target for Muscle Regeneration

Foxk1-AS could be a potential therapeutic target for promoting muscle regeneration in conditions such as muscular dystrophy or age-related muscle loss.

Understanding Muscle Development

This research provides insights into the complex regulatory networks governing muscle development and regeneration, specifically highlighting the role of natural antisense RNAs.

Gene Therapy Strategies

The findings suggest that manipulating the expression of Foxk1-AS could be a viable gene therapy strategy for repairing damaged muscle fibers.

Natural antisense RNA Foxk1‑AS promotes myogenic differentiation by inhibiting Foxk1 activity

Simple Explanation

Key Findings

Research Summary

Practical Implications

Therapeutic Target for Muscle Regeneration

Understanding Muscle Development

Gene Therapy Strategies

Study Limitations

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Was this summary helpful?

Natural antisense RNA Foxk1‑AS promotes myogenic differentiation by inhibiting Foxk1 activity

Simple Explanation

Key Findings

Research Summary

Practical Implications

Therapeutic Target for Muscle Regeneration

Understanding Muscle Development

Gene Therapy Strategies

Study Limitations

Your Feedback

Was this summary helpful?