MicroRNAs are essential for development and function of inner ear hair cells in vertebrates
MicroRNAs are essential for development and function of inner ear hair cells in vertebrates
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DOI：
10.1073/pnas.0812446106
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发表时间：
2009-05-12
影响因子：
11.1
通讯作者：
Avraham, Karen B.
中科院分区：
文献类型：
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作者：
Friedman, Lilach M.;Dror, Amiel A.;Avraham, Karen B.
MicroRNAs （miRNAs）抑制靶mrna的翻译，并直接或间接影响大部分蛋白质编码基因的表达。本研究的重点是小鼠耳蜗和前庭（内耳的两个腔室）中表达的miRNAs。Dicer1的条件敲除小鼠表明，mirna对内耳功能性毛细胞的产后存活至关重要。通过结合miRNA转录组分析、时空表达模式和生物信息学，我们确定了在脊椎动物内耳发育中起作用的miRNA。微阵列在新生小鼠全耳蜗和前庭中发现了相似的miRNA谱，但六种miRNA （miR-15a、miR-18a、miR-30b、miR-99a、miR-182和miR-199a）不同的时空表达模式可能反映了它们的作用。其中两个mirna， miR-15a-1和miR-18a，也被证明对斑马鱼内耳发育和形态发生至关重要。为了提出可能被选定的mirna抑制翻译的目标mRNA，我们结合了基于生物信息学的预测和mRNA表达数据。最后，我们提出间接证据表明Slc12a2、Cldn12和Bdnf mrna可能是miR-15a的靶点。我们的数据支持这样的假设：小鼠和斑马鱼的内耳组织分化和维持是由一组保守的细胞特异性mirna调控的。
MicroRNAs (miRNAs) inhibit the translation of target mRNAs and affect, directly or indirectly, the expression of a large portion of the protein-coding genes. This study focuses on miRNAs that are expressed in the mouse cochlea and vestibule, the 2 inner ear compartments. A conditional knock-out mouse for Dicer1 demonstrated that miRNAs are crucial for postnatal survival of functional hair cells of the inner ear. We identified miRNAs that have a role in the vertebrate developing inner ear by combining miRNA transcriptome analysis, spatial and temporal expression patterns, and bioinformatics. Microarrays revealed similar miRNA profiles in newborn-mouse whole cochleae and vestibules, but different temporal and spatial expression patterns of six miRNAs (miR-15a, miR-18a, miR-30b, miR-99a, miR-182, and miR-199a) may reflect their roles. Two of these miRNAs, miR-15a-1 and miR-18a, were also shown to be crucial for zebrafish inner ear development and morphogenesis. To suggest putative target mRNAs whose translation may be inhibited by selected miRNAs, we combined bioinformatics-based predictions and mRNA expression data. Finally, we present indirect evidence that Slc12a2, Cldn12, and Bdnf mRNAs may be targets for miR-15a. Our data support the hypothesis that inner ear tissue differentiation and maintenance are regulated and controlled by conserved sets of cell-specific miRNAs in both mouse and zebrafish.