Abstract for presentation at 11th International Congress of Human Genetics

Approximately 98% of transcribed RNA in mammalian cells does not code for proteins. This large fraction of RNA consists of introns of protein-coding genes and both exons and introns of non-protein-coding genes. It was recently noticed that these non-protein-coding RNAs (ncRNA) have important regulatory roles on the expression of protein-coding cells and are associated with human disease. MicroRNAs (miRNAs) comprise one the most prominent classes of ncRNAs. These 17-24 nucleotide-long molecules are derived from endogenous short hairpin precursor structures (pre-miRNAs, 60-124 nt) that are processed from longer RNA molecules (pri-miRNAs) transcribed from miRNA genes. Hearing loss due to genetic mutations affects approximately 60% of persons with a form of hearing impairment. Until now, only protein-coding genes or genes for tRNAs or rRNAs have been linked to hereditary deafness. Over 40 protein-coding chromosomal genes and more then a dozen tRNA/rRNA-coding mitochondrial genes have been linked to non-syndromic hearing loss (NSHL) in humans, Congenital or early onset deafness often involves developmental defects of portions of the inner ear. Genes required for mechanosensory transduction and development of the inner ear are tightly regulated by a cascade of transcription factors, only a portion of which are known today. Several of these genes are directly involved in deafness. An additional level of regulation may be provided by non-coding regulatory RNAs. Our goal has been to identify miRNAs that contribute to the development and function of the mouse inner ear and may be involved in hearing and deafness in mammals, as well as their target mRNAs. We used bioinformatics and other prediction tools to identify potential miRNAs that may control inner ear development or function. Using methods to profile the microRNA of the mouse inner ear, we have evaluated the expression of candidate miRNAs in the cochlea.