Figure 4.

Pathogenic mutation of miR-140 in skeletal dysplasia and ceRBP effects.

(Cited and modified from Grigelioniene G, Suzuki HI, Taylan F, et al. Gain-of-function mutation of microRNA-140 in human skeletal dysplasia. Nat Med. 2019;25(4):583-90⁽⁷⁵⁾ and Suzuki HI, Spengler RM, Grigelioniene G, et al. Deconvolution of seed and RNA-binding protein crosstalk in RNAi-based functional genomics. Nat Genet. 2018;50(5):657-61⁽⁷⁶⁾. Copyright of the figure belongs to the authors.)

A seed region mutation in chondrocyte-specific miR-140 has been identified in spondyloepiphyseal dysplasia MIR140 type Nishimura (OMIM #618618). This mutation results in widespread derepression of wild-type miR-140-5p targets and repression of mutant miR-140-5p (miR-140-5p-G) targets. Additionally, the miR-140-5p mutant seed competes with the Ybx1 RNA-binding protein for the overlapping binding sites.