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.

MiRNA-21

“…Chemo resistant-related miR-21-targets are definitely not just one or two, but rather a series of factors. Moreover, since miRNA regulates the target gene expression either by translational suppression or by mRNA destabilization of mRNAs with imperfect complementary sequences, common in mammals, 46 attention on transcriptional level of these targets is also essential. Therefore, further study focused on more targets and their regulatory network is required in the near future.…”

Molecular Mechanisms of Inner Ear Development

“…Although the sequence of each miRNA can be used to predict which UTRs it will bind to, these predictions are imperfect, making it difficult to identify which genes will be regulated by a particular miR-NA. At least 100 miRNAs are expressed in the developing cochlea (Elkan-Miller et al 2011). Most experimental work has been focused on the miR-183 family, which contains three members, miR-96, miR-182, and miR-183 (Li and Fekete 2010;Weston et al 2011).…”

MicroRNA sequencing and molecular mechanisms analysis of the effects of gold nanoparticles on human dermal fibroblasts

“…Medical studies have begun to explore the reasons for the differences in mRNA and protein expression levels in cells via gene expression regulation [23]. In the process of transferring genetic information from DNA to RNA to protein, RNA serves as more than just a bridge.…”

“…A subset of small non-coding RNAs, including microRNA, siRNA, piRNA and esiRNA, etc., constitute a regulatory network that regulates gene expression at the transcriptional and post-transcriptional levels and is involved in a wide range of physiological processes such as cell proliferation, differentiation, and apoptosis, and so on [24]. Elkan-Miller et al investigated the mRNA, miRNA and protein expression profiles in cochlear and vestibular hair cells and identified miRNA-target pairs, and reporting that the greatest differentially expressed miRNA, miR135b, regulated PSIP1-P75 by translational suppression [23].…”