Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss
| Autor: | Leticia Olavarrieta, Matías Morín, Tamas Dalmay, Nick Redshaw, Karen P. Steel, Ángeles Mencía, Ignacio del Castillo, Felipe Moreno, Fernando Mayo-Merino, Luis A. Aguirre, Silvia Modamio-Høybjør, M A Moreno-Pelayo |
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| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | Nature Genetics. 41:609-613 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng.355 |
| Popis: | Miguel Moreno-Pelayo and colleagues report mutations in the seed region of human miR-96 segregating with progressive hearing loss in two families. In an accompanying paper, Karen Steel and colleagues show that the mouse diminuendo mutant, which also shows progressive hearing loss, carries a similar mutation in the seed region of mouse miR-96. 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. |
| Databáze: | OpenAIRE |
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