Gain-of-function mutation of microRNA-140 in human skeletal dysplasia.

ABSTRACT: MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression. Heterozygous loss-of-function point mutations of miRNA genes are associated with several human congenital disorders^1-5, but neomorphic (gain-of-new-function) mutations in miRNAs due to nucleotide substitutions have not been reported. Here we describe a neomorphic seed region mutation in the chondrocyte-specific, super-enhancer-associated MIR140 gene encoding microRNA-140 (miR-140) in a novel autosomal dominant human skeletal dysplasia. Mice with the corresponding single nucleotide substitution show skeletal abnormalities similar to those of the patients but distinct from those of miR-140-null mice⁶. This mutant miRNA gene yields abundant mutant miR-140-5p expression without miRNA-processing def

SUBMITTER: Grigelioniene G 

PROVIDER: S-EPMC6622181 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature