Integration of Transcriptomics, Proteomics, and MicroRNA Analyses Reveals Novel MicroRNA Regulation of Targets in the Mammalian Inner Ear

PLoS One

Karen B. Avraham¹  Igor Ulitsky¹  Anya Rudnicki²  Amiel A. Dror²  Danielle R. Lenz²  Ronna Hertzano²  Ran Elkon²  Tal Elkan-Miller²  Martin Irmler³  Johannes Beckers³  Ron Shamir⁴ 

[1] Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel;Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;Helmholtz Centre Munich, German Research Center for Environmental Health (GmbH), Institute of Experimental Genetics, Neuherberg/Munich, Germany;Technical University Munich, Center of Life and Food Sciences Weihenstephan, Freising, Germany

关键词: MicroRNAs;    Inner ear;    Cochlea;    Gene expression;    Protein expression;    Microarrays;    Vestibular hair cells;    Messenger RNA;   

DOI  :  10.1371/journal.pone.0018195

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY