Integration of transcriptomics, proteomics, and microRNA analyses reveals novel microRNA regulation of targets in the mammalian inner ear.
Integration of transcriptomics, proteomics, and microRNA analyses reveals novel microRNA regulation of targets in the mammalian inner ear.
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DOI：
10.1371/journal.pone.0018195
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发表时间：
2011-04-05
期刊：
影响因子：
3.7
通讯作者：
Avraham KB
中科院分区：
文献类型：
--
作者：
Elkan-Miller T;Ulitsky I;Hertzano R;Rudnicki A;Dror AA;Lenz DR;Elkon R;Irmler M;Beckers J;Shamir R;Avraham KB
我们采用了一种新的方法来识别功能重要的microRNA（miRNA）-靶相互作用，整合miRNA，转录组和蛋白质组谱，并使用FAME算法进行先进的计算机分析。由于miRNA在内耳中发挥着至关重要的作用，导致人类和小鼠耳聋的miRNA突变的发现证明了这一点，我们将这种方法应用于显微解剖的听觉和前庭感觉上皮。我们检测了157个miRNAs在内耳感觉上皮中的表达，其中53个miRNAs在耳蜗和前庭之间差异表达。通过在转录物和蛋白质数据集中搜索富集或耗尽的靶标来确定功能重要的miRNA，其表达与miRNA调控的法则一致。重要的是，相当多的靶点仅在蛋白质数据集中检测到，这归因于翻译抑制的调节。我们鉴定并实验验证了前庭毛细胞中miR-135 b对PSIP 1-P75的调节，PSIP 1-P75是一种以前在内耳中未知的转录共激活因子。我们的研究结果表明，miR-135 b作为一种细胞效应器，参与调节耳蜗和前庭毛细胞之间的一些差异。
We have employed a novel approach for the identification of functionally important microRNA (miRNA)-target interactions, integrating miRNA, transcriptome and proteome profiles and advanced in silico analysis using the FAME algorithm. Since miRNAs play a crucial role in the inner ear, demonstrated by the discovery of mutations in a miRNA leading to human and mouse deafness, we applied this approach to microdissected auditory and vestibular sensory epithelia. We detected the expression of 157 miRNAs in the inner ear sensory epithelia, with 53 miRNAs differentially expressed between the cochlea and vestibule. Functionally important miRNAs were determined by searching for enriched or depleted targets in the transcript and protein datasets with an expression consistent with the dogma of miRNA regulation. Importantly, quite a few of the targets were detected only in the protein datasets, attributable to regulation by translational suppression. We identified and experimentally validated the regulation of PSIP1-P75, a transcriptional co-activator previously unknown in the inner ear, by miR-135b, in vestibular hair cells. Our findings suggest that miR-135b serves as a cellular effector, involved in regulating some of the differences between the cochlear and vestibular hair cells.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
2.8
作者：
Kawamoto K;Izumikawa M;Beyer LA;Atkin GM;Raphael Y
通讯作者：
Raphael Y
影响因子：
3.4
作者：
Chylack, LT;Fu, L;Goldstein, LE
通讯作者：
Goldstein, LE
影响因子：
7
作者：
Griffin, TJ;Gygi, SP;Aebersold, R
通讯作者：
Aebersold, R
影响因子：
56.9
作者：
Farh, KKH;Grimson, A;Bartel, DP
通讯作者：
Bartel, DP