A4 - Light-induced dynamic miRNA decay in photoreceptor cells

Non-coding miRNAs are important regulators of gene expression. However, many aspects of their biogenesis such as metabolic turnover are still enigmatic. A decade ago, we identified a miRNA cluster, consisting of miR-183/96/182, which is highly and, surprisingly, very dynamically expressed in retinal photoreceptor cells. In light, the expression of the cluster is upregulated suggesting an activity-dependent transcriptional activation. In darkness, the expression levels of the pri-miRNA transcript and the mature miRNA decreased by 50%. Our data suggest the presence of a rapid pri-miRNA decay pathway on top of transcriptional inhibition upon dark adaptation. Quantitatively, this cluster represents 2/3 of the photoreceptor miRNA content and was found essential for proper photoreceptor physiology. Here, we aim to identify the proteins bound to miR-183/96/182 in darkness and study how these mediate the dynamic miRNA decay in dark-adapted photoreceptor cells. Finally, we will also study the impact of secondary pri-miR-183/96/182 structures on its decay. These activity-dependent aspects of miRNA turn-over are essential to understand the full miRNA biogenesis, regulation, and function within mammalian photoreceptors but very likely also represent a general, although still unknown, miRNA feature.