Molecular Biology

RNA Silencing

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Science  24 Apr 2009:
Vol. 324, Issue 5926, pp. 440
DOI: 10.1126/science.324_440c
CREDIT: AGNIESZKA RZADZINSKA, NAT. GENET. 10.1038/NG.369; 10.1038/NG.355 (2009)

Progressive hearing loss is a common disorder that appears to arise from a diverse range of genetic mechanisms, probably reflecting the anatomical and functional complexity of the human ear. Two studies of mice and humans with hearing loss have converged on a pathogenic mutation that is distinct from the 50 previously characterized mutations in that it affects a small regulatory RNA rather than a protein-coding gene.

In a genetic screen for hearing-impaired mice, Lewis et al. identified a mutation that, when present in heterozygous form, caused abnormalities of inner and outer hair cells [sensory receptors in the ear that are critical for hearing; wild-type (left) and heterozygous (right) inner cells are shown above] and progressive hearing loss beginning when the mice were 4 to 6 weeks old. The mutation resides within the functional “seed” region of a microRNA called miR-96 that is expressed in hair cells and that, like other microRNAs, is presumed to bind to and alter the expression of protein-coding messenger RNAs. Supporting the causal role of miR-96 in hearing loss, Mencia et al. found that two Spanish families with inherited progressive hearing loss harbored mutations in the seed region of the same microRNA and that these mutations impaired the processing of the RNA to its mature form.

Nat. Genet. 10.1038/ng.369; 10.1038/ng.355 (2009).

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