Regulatory Non-Coding RNAs in the Auditory System

Einat Rosen ¹ Tal Koffler-Brill * ¹ Shahar Taiber ¹ Rebecca Haffner ² Alejandro Anaya ³ Likhitha Kolla ³ Matthew W. Kelley ³ Igor Ulitsky ⁴ Karen B. Avraham ¹

¹department of Human Molecular Genetics & Biochemistry, Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Israel
²Department of Veterinary Resources, Weizmann Institute of Science, Israel
³Section on Developmental Neuroscience, National Institute on Deafness and Other Communication Disorders, Nih, USA
⁴Department of Biological Regulation, Weizmann Institute of Science, Israel

Pathogenic variants in the coding regions of over 100 genes are associated with hereditary deafness. As we have not solved the cause of deafness in our entire cohort of families with hearing loss, we predict that some cases will be due to variants in the non-coding region of the genome. Some of these may include non-coding RNAs and specifically, long non-coding RNAs (lncRNAs), which are longer than 200bp and play a critical role in gene regulation. In our study, we are attempting to decode the function and mechanism of different lncRNAs that may have a role in gene regulation in the inner ear. We are studying lncRNAs using cell lines and mouse tissues, and both bioinformatic and experimental analysis. The expression and localization of a subset of lncRNAs was determined using RT-PCR, RNAscope, single cell RNA-seq and cellular fractionation. We have also created lncRNA knock-out transgenic mice, using the CRISPR-Cas9 genome editing method. The lncRNAs we chose are expressed in the greater epithelial ridge in the inner ear, and our work will help us reveal their role in inner ear function and development. Funded by the Israel Science Foundation (ISF) Grant no. 2033/16 to KBA. *Contributed equally.