Figure 1

miR-486 is a highly conserved mammalian miRNA that is differentially expressed in DMD skeletal muscle. (A) miR-486 is conserved across mammals and is under the transcriptional regulation of the ankyrin 1 locus. The ANK1.5 isoform has a unique start exon (exon 39A; blue) that is transcribed independently of the ANK1.1 isoform and lacks the ankyrin repeat domain. (B) miR-486 is significantly reduced in DMD human skeletal muscle biopsies, but not in the milder BMD muscle biopsies, as compared to normal muscle controls. P = 0.03. The y-axis represents mature miR-486 fold levels normalized to U6 snRNA housekeeping controls. Error bars indicate SEM. Normal biopsies: n = 5, DMD biopsies: n = 5 and BMD biopsies: n = 3. (C) miR-486 is significantly upregulated during normal human myogenic differentiation, while the DMD myoblasts express miR-486 at significantly lower levels. The y-axis represents mature miR-486 fold levels normalized to U6 snRNA loading controls, and the x-axis represents the time of myogenic differentiation from 50% confluency (proliferating myoblasts) until day 4 differentiation (multinucleated myotube formation). At 90% confluency (day 0 differentiation), myoblasts were exposed to differentiation medium (2% horse serum). Blue lines represent normal human myoblasts, and red lines represent DMD myoblasts. (D) miR-486 is upregulated during skeletal muscle regeneration following CTX-induced TA muscle injury. Blue lines indicate wild-type C57B6/J mice, and red bars indicate mdx^5cv mice. The y-axis represents mature miR-486 fold levels normalized to U6 snRNA housekeeping controls. Error bars indicate SEM. *P < 0.005 and **P < 0.05.