Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss

作者：Mencia Angeles; Modamio Hoybjor Silvia; Redshaw Nick; Morin Matias; Mayo Merino Fernando; Olavarrieta Leticia; Aguirre Luis A; del Castillo Ignacio; Steel Karen P; Dalmay Tamas; Moreno Felipe; Angel Moreno Pelayo Miguel

来源：Nature Genetics, 2009, 41(5): 609-613.

DOI：10.1038/ng.355

MicroRNAs (miRNAs) bind to complementary sites in their target mRNAs to mediate post-transcriptional repression(1,2), with the specificity of target recognition being crucially dependent on the miRNA seed region(3). Impaired miRNA target binding resulting from SNPs within mRNA target sites has been shown to lead to pathologies associated with dysregulated gene . However, no pathogenic mutations within the mature sequence of a miRNA have been reported so far. Here we show that point mutations in the seed region of miR-96, a miRNA expressed in hair cells of the inner ear(8), result in autosomal dominant, progressive hearing loss. This is the first study implicating a miRNA in a mendelian disorder. The identified mutations have a strong impact on miR-96 biogenesis and result in a significant reduction of mRNA targeting. We propose that these mutations alter the regulatory role of miR-96 in maintaining gene expression profiles in hair cells required for their normal function.

• 出版日期2009-5