Edited microRNA-21-5p (miR-21-5p (I))

The fibrosis-protective microRNA isomiR refers to a specific isoform of microRNA-21-5p (miR-21-5p) that is generated through adenosine-to-inosine (A-to-I) RNA editing by the enzyme ADAR1. While the canonical miR-21-5p is a well-known pro-fibrotic factor that promotes the activation of fibroblasts and the deposition of extracellular matrix in organs like the heart, liver, and kidneys, its edited counterpart possesses a distinct seed sequence. This change in the seed region causes the isomiR to target a different set of messenger RNAs, effectively switching its function from promoting fibrosis to protecting against it. In the context of cardiovascular and chronic inflammatory diseases, the balance between canonical and edited miR-21-5p is a critical determinant of disease progression. Therapeutic strategies aimed at increasing the levels of this protective isomiR, either by enhancing ADAR1 activity or by delivering synthetic isomiR mimics, are being explored as novel treatments for fibrotic disorders. This target represents a sophisticated example of how post-transcriptional modifications can radically alter the biological impact of a single genetic locus, offering a precise lever for pharmacological intervention in tissue remodeling.

Other names

Edited miR-21miR-21-5p isomiRA-to-I edited miR-21-5pFibrosis-protective isomiR

The edited isomiR of miR-21-5p (generated by ADAR1-mediated A-to-I editing) shifts its target repertoire from pro-fibrotic genes to anti-fibrotic pathways. Unlike the canonical miR-21-5p, which promotes fibrosis by targeting PTEN and SPRY1, the edited version (miR-21-5p (I)) targets pro-fibrotic factors, thereby exerting a protective effect against tissue remodeling and collagen deposition.