Letter abstract
Nature Genetics
Published online: 12 April 2009 | doi:10.1038/ng.355
Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss
Ángeles Mencía1,2, Silvia Modamio-Høybjør1,2, Nick Redshaw3, Matías Morín1,2, Fernando Mayo-Merino1,2, Leticia Olavarrieta1,2, Luis A Aguirre1,2, Ignacio del Castillo1,2, Karen P Steel4, Tamas Dalmay3, Felipe Moreno1,2 & Miguel Ángel Moreno-Pelayo1,2
MicroRNAs (miRNAs) bind to complementary sites in their target mRNAs to mediate post-transcriptional repression1, 2, with the specificity of target recognition being crucially dependent on the miRNA seed region3. Impaired miRNA target binding resulting from SNPs within mRNA target sites has been shown to lead to pathologies associated with dysregulated gene expression4, 5, 6, 7. 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 ear8, 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.
- Unidad de Genética Molecular, Hospital Ramón y Cajal, Madrid, Spain.
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain.
- School of Biological Sciences, University of East Anglia, Norwich, UK.
- Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
Correspondence to: Miguel Ángel Moreno-Pelayo1,2 e-mail: mmoreno.hrc@salud.madrid.org