Dynamic m 6 A mRNA Methylation Reveals the Role of METTL3/14-m 6 A-MNK2-ERK Signaling Axis in Skeletal Muscle Differentiation and Regeneration
Xie SJ., Lei H., Yang B., Diao LT., Liao JY., He JH.
Laboratory Study, published in Front Cell Dev Biol (2021) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Laboratory Study
- Journal
- Front Cell Dev Biol (2021)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 34660602
- PMCID
- PMC8517268
- DOI
- 10.3389/fcell.2021.744171
- Citations
- 35
Abstract (original English)
N 6 -methyladenosine (m 6 A) RNA methylation has emerged as an important factor in various biological processes by regulating gene expression. However, the dynamic profile, function and underlying molecular mechanism of m 6 A modification during skeletal myogenesis remain elusive. Here, we report that members of the m 6 A core methyltransferase complex, METTL3 and METTL14, are downregulated during skeletal muscle development. Overexpression of either METTL3 or METTL14 dramatically blocks myotubes formation. Correspondingly, knockdown of METTL3 or METTL14 accelerates the differentiation of skeletal muscle cells. Genome-wide transcriptome analysis suggests ERK/MAPK is the downstream signaling pathway that is regulated to the greatest extent by METTL3/METTL14. Indeed, METTL3/METTL14 expression facilitates ERK/MAPK signaling. Via MeRIP-seq, we found that MNK2, a critical regulator of ERK/MAPK signaling, is m 6 A modified and is a direct target of METTL3/METTL14. We further revealed that YTHDF1 is a potential reader of m 6 A on MNK2, regulating MNK2 protein levels without affecting mRNA levels. Furthermore, we discovered that METTL3/14-MNK2 axis was up-regulated notably after acute skeletal muscle injury. Collectively, our studies revealed that the m 6 A writers METTL3/METTL14 and the m 6 A reader YTHDF1 orchestrate MNK2 expression posttranscriptionally and thus control ERK signalin
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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