Abstract
Long non-coding RNAs (lncRNAs) have been implicated in fundamental and diverse biological processes, including myogenesis. However, the molecular mechanisms involved in this process remain largely unexplored. This study found that H19 affected the differentiation of porcine satellite cells (PSCs) by directly binding to the DNA/RNA-binding protein TDP43. Functional analyses showed that TDP43 knockdown decreased PSC differentiation, whereas TDP43 overexpression exerted opposite effects in vitro. Furthermore, rescue experiments demonstrated that TDP43 can rescue the decrease in PSC differentiation caused by H19 knockdown. Mechanistically, H19 may act as a scaffold to recruit TDP43 to the promoters of MYOD and thereby activate the transcription of MYOD, leading to PSC differentiation. In summary, we elucidate the molecular mechanism by which H19 and TDP43 regulate myogenesis.
Highlights
Myogenesis is the process of skeletal muscle development and formation, which is a highly coordinated developmental process involving the coordinate expression of a number of myogenic regulatory factors, such as paired box 3, paired box 7, myogenic factor 5, myogenin, and myogenic differentiation (MYOD) [1,2,3]
Our studies showed that H19 was present in the nucleus and the cytoplasm (Figure 1A)
The biotinylated H19 and biotinylated antisense H19 were incubated with porcine satellite cells (PSCs) cell lysates, and their interacting proteins were captured by streptavidin beads and subjected to mass spectrometry (MS)
Summary
Myogenesis is the process of skeletal muscle development and formation, which is a highly coordinated developmental process involving the coordinate expression of a number of myogenic regulatory factors, such as paired box 3, paired box 7, myogenic factor 5, myogenin (myog), and myogenic differentiation (MYOD) [1,2,3]. Sirt AS lncRNA, an lncRNA transcribed from the Sirt antisense strand, attenuates the inhibition of miR-34a to Sirt translation to accelerate myoblast proliferation and represses myoblast differentiation It interacts with Sirt mRNA forming RNA duplex to promote Sirt translation [21]. H19 is a lncRNA that plays an essential role during myogenic differentiation [22,23,24] It is a highly abundant transcript in skeletal muscle and it is upregulated in the process of myoblast differentiation and muscle regeneration. H19 can regulate the differentiation of PSCs through competitive binding with miRNA and directly binding with a cytoplasmic protein (unpublished) Considering that both are expressed in the nucleus and the cytoplasm, we inferred that. H19 may act as a scaffold to recruit TDP43 to the promoter region of MYOD in PSCs and thereby activate the transcription of MYOD, leading to PSC differentiation
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