Non-coding RNA regulation in the mammalian inner ear

Hearing loss and deafness are among the most common sensory disabilities, with most known cases caused by pathogenic genetic variants that lead to loss and degradation of hair cells. Non-coding RNA (ncRNA) are crucial for cell development and maturation, and play a major regulatory role in the development and maturation of the mammalian inner ear. Advances in high-throughput sequencing are enabling us to study the role of ncRNAs in the auditory field, while using small amounts of inner ear sensory epithelium as input. We are investigating different levels of regulation including transcription factors and ncRNA, such as microRNA (miRNA) and long non-coding RNA (lncRNA). These regulations are being examined at two different time points during the development of the mouse inner ear sensory epithelium, embryonic day 16.5 (E16.5) and post-natal day 0 (P0). We have identified hundreds of miRNAs expressed in the mouse inner ear vestibule and cochlea at these two different time points (Rudnicki, Isakov et al. BMC Genomics 2014). Of these, miR-34c and miR-449a are predicted to target Atoh1, a transcription factor essential for the development and formation of inner ear hair cells. By studying the different regulatory levels of ncRNA, we will be able to discover gene specific and systematic modes of gene expression and regulation, allowing us to gain a better understanding of inner ear development and maturation. Funded by the Israel Science Foundation (ISF) Grant no. 2033/16 to KBA.