A-to-I RNA editing impairs miR-376b-3p repression of RYBP in skeletal muscle satellite cells

TL;DR

This study shows that RNA editing in miR-376b-3p reduces its ability to control muscle cell development by affecting its target RYBP.

Contribution

The study reveals how A-to-I RNA editing alters miR-376b-3p function in skeletal muscle satellite cells.

Findings

miR-WT promotes muscle cell proliferation and differentiation by targeting RYBP.

miR-E, the edited form, fails to target RYBP and lacks promyogenic activity.

Adenosine-to-inosine editing impairs miR-376b-3p's regulatory role in muscle development.

Abstract

Adenosine-to-inosine RNA editing can affect miRNA activity, but its role in skeletal muscle development remains unclear. Here, we investigated miR-376b-3p in goat skeletal muscle satellite cells (MuSCs), which undergo adenosine deaminase acting on RNA 1–mediated editing at the sixth nucleotide of its seed sequence. Although both isoforms were detected, the unedited miR-376b-3p (miR-WT) predominated over the edited form (miR-E) during skeletal muscle development and MuSC differentiation. Functional assays revealed that miR-WT, but not the miR-E type, enhanced MuSC proliferation and differentiation by upregulating Pax7, PCNA, MyoD, MyoG, and MyHC, and promoting myotube formation. Furthermore, we identified Ring1 and YY1 binding protein (RYBP), a repressor of myogenesis, as a direct target of miR-WT. Overexpression of RYBP inhibited MuSC differentiation, whereas miR-WT relieved this repression through direct binding to the RYBP 3′UTR. In contrast, miR-E failed to target RYBP and lacked promyogenic activity. These findings demonstrate that adenosine-to-inosine editing attenuates the function of miR-376b-3p, highlighting its role as a post-transcriptional regulator of skeletal muscle development.

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