title: Integration of transcriptomics, proteomics, and microRNA analyses reveals novel microRNA regulation of targets in the mammalian inner ear.
abstract: 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.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Elkan-Miller
authors.forename: Igor
authors.initials: I
authors.lastname: Ulitsky
authors.forename: Ronna
authors.initials: R
authors.lastname: Hertzano
authors.forename: Anya
authors.initials: A
authors.lastname: Rudnicki
authors.forename: Amiel A
authors.initials: AA
authors.lastname: Dror
authors.forename: Danielle R
authors.initials: DR
authors.lastname: Lenz
authors.forename: Ran
authors.initials: R
authors.lastname: Elkon
authors.forename: Martin
authors.initials: M
authors.lastname: Irmler
authors.forename: Johannes
authors.initials: J
authors.lastname: Beckers
authors.forename: Ron
authors.initials: R
authors.lastname: Shamir
authors.forename: Karen B
authors.initials: KB
authors.lastname: Avraham
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003051:Cochlea / Q000378:metabolism; D015536:Down-Regulation; D007758:Ear, Inner / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009928:Organ Specificity; D040901:Proteomics / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018511:Systems Integration; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014722:Vestibule, Labyrinth / Q000166:cytology / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D035683:MicroRNAs; C549289:Mirn135 microRNA, mouse; C504650:Psip1 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors