Biogenesis and Function of RNA Polymerase III transcript-derived piRNAs in Neuroblastoma (B14*)

• Subject Area: Biochemistry
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 185476941

RNA-induced gene silencing of transposable elements by piRNA (PIWI-interacting RNA) protects the genomic integrity of germ cells. More recently, the expression of piRNA and PIWI proteins has been associated with cancer, however, the mechanism and function of piRNA biogenesis and piRNA-induced gene silencing in cancer is not well understood. Our preliminary studies demonstrate that cancer-associated RNA-binding protein La (LARP3) is overexpressed in neuroblastoma and that shRNA-mediated depletion of La, which binds to the 3’-end of all RNA Polymerase (Pol) III transcripts, increases the expression of Pol III transcript-derived piRNAs in neuroblastoma cells. Furthermore, RNA-Seq revealed that the increase of those piRNAs correlates with reduced expression of predicted target mRNAs. In our model overexpression of La protein diminishes RNA Pol III transcript-derived piRNA biogenesis, reduces piRNA-induced gene silencing and consequently promotes cancer progression. Hence, this new project aims to study the biogenesis of piRNA, the piRNP composition, and the cellular impact of piRNA RNPs on gene expression in neuroblastoma cells.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 960: Ribosome Formation: Principles of RNP Biogenesis and Control of their Function
• Applicant Institution: Universität Regensburg
• Project Heads: Tilman Heise, Ph.D.; Dr. Gunhild Sommer