Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom.
Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2355-60. doi: 10.1073/pnas.1016646108. Epub 2011 Jan 18.
MicroRNAs (miRNAs) are small noncoding RNAs able to regulate a broad range of protein-coding genes involved in many biological processes. miR-96 is a sensory organ-specific miRNA expressed in the mammalian cochlea during development. Mutations in miR-96 cause nonsyndromic progressive hearing loss in humans and mice. The mouse mutant diminuendo has a single base change in the seed region of the Mir96 gene leading to widespread changes in the expression of many genes. We have used this mutant to explore the role of miR-96 in the maturation of the auditory organ. We found that the physiological development of mutant sensory hair cells is arrested at around the day of birth, before their biophysical differentiation into inner and outer hair cells. Moreover, maturation of the hair cell stereocilia bundle and remodelling of auditory nerve connections within the cochlea fail to occur in miR-96 mutants. We conclude that miR-96 regulates the progression of the physiological and morphological differentiation of cochlear hair cells and, as such, coordinates one of the most distinctive functional refinements of the mammalian auditory system.
微小 RNA（miRNAs）是一类能够调节广泛涉及多种生物学过程的蛋白质编码基因的小非编码 RNA。miR-96 是一种在哺乳动物耳蜗发育过程中特异性表达的感觉器官特异性 miRNA。miR-96 的突变会导致人类和小鼠的非综合征性进行性听力损失。小鼠突变体 diminuendo 在 Mir96 基因的种子区域发生单个碱基改变，导致许多基因的表达广泛改变。我们利用这种突变体来探索 miR-96 在听觉器官成熟过程中的作用。我们发现，突变体感觉毛细胞的生理发育在出生前后的某一天被阻止，此时它们尚未进行内外毛细胞的生物物理分化。此外，miR-96 突变体中毛细胞静纤毛束的成熟和耳蜗内听神经连接的重塑未能发生。我们得出结论，miR-96 调节耳蜗毛细胞的生理和形态分化的进展，因此协调了哺乳动物听觉系统最具特色的功能细化之一。
