microRNA 431 (miR-431)

microRNA 431 (miR-431) is a conserved, small non-coding RNA transcribed from the antisense strand of the imprinted gene RTL1 and processed as part of several miRNAs in this locus. It regulates gene expression post-transcriptionally and is predominantly expressed in neural and skeletal muscle tissues, where it plays roles in axon regeneration (via targeting Kremen1 and modulating Wnt/beta-catenin signaling), muscle differentiation and regeneration (by silencing Pax7 and SMAD4, key factors in stem cell self-renewal and TGF-β signaling). Age-associated decline of miR-431 impairs muscle regeneration, while supplementation restores regenerative potential. These findings identify miR-431 as a promising therapeutic target for neuromuscular diseases, muscle aging, and potentially for injury recovery; however, there are no approved drugs targeting miR-431 and its safety as a therapeutic remains under basic research investigation.

Other names

hsa-miR-431MIR431MIRN431miRNA431mir-431microRNA-431

Gene silencing through binding to 3′ untranslated regions (UTRs) of target mRNAs (Kremen1, Pax7, SMAD4), leading to mRNA degradation or translational inhibition. Downregulation of antagonists or signaling suppressors to promote regeneration (e.g., silencing Wnt pathway inhibitor Kremen1). Modulation of TGF-β signaling pathway via direct targeting of SMAD4, reducing its protein levels and alleviating inhibitory effects on muscle differentiation.