The Role of Noncoding RNAs in Eye Function and Disease and the study of the molecular basis of eye inherited disorders

Inherited eye diseases are a common cause of visual impairment in children and young adults. The molecular causes of a significant fraction of a large variety of ocular genetic disorders recognized thus far have not been elucidated yet. In particular, we are interested in understanding the pathogenic mechanisms underlying inherited retinal disorders, including retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) and eye developmental anomalies such as microphthalmia, anophtalmia and coloboma. We are currently focusing on elucidating the role of microRNAs in eye development and function. MicroRNAs are small, endogenous RNAs that negatively regulate gene expression post-transcriptionally by binding to target sites in the 3’ untranslated region (UTR) of messenger RNAs. Our data provide examples of how a specific miRNA can regulate multiple events in eye formation. To gain insight on the function of specific microRNAs it is important to identify their mRNA targets. Towards this goal, we first developed the HocTAR tool, which recognized the targets of intragenic microRNAs by combining the expression analysis of their host genes and sequence prediction softwares (http://hoctar.tigem.it). More recently, we further exploited the integration of co-expression data analysis and of target prediction and implemented the co-expression Meta-analysis of miRNA Targets (CoMeTa) tool to gain insight into the biological functions of miRNAs and to provide a comprehensive, genome-wide scale analysis of human miRNA regulatory networks. Identification of mRNA targets is key to gaining insight of the function of specific microRNAs. Towards this goal, we also developed a novel strategy combining expression data analysis and sequence prediction softwares. The "Total Award" amount indicated for this project represents the share of the funding of the Telethon Foundation for research by the Tigem institute from July 2016 until last budget year, calculated based on the size of the research group.