It is my great pleasure to invite you to the next Nencki Institute Seminar which will take place at 3pm on the 20th of January. Prof. Gracjan Michlewski, head of the Dioscuri Centre for Laboratory of RNA-Protein Interactions at the International Institute of Molecular and Cell Biology in Warsaw, will give a lecture entitled: Regulation of microRNA biogenesis and alpha-Syn levels involved in Parkinson’s disease.
MicroRNAs (miRs) are small noncoding RNAs that negatively regulate the expression of mRNAs. Due to the important role of miRNAs organism development, function, and disease the production of mature miRNAs is tightly regulated at multiple levels, including transcriptional and post-transcriptional steps. We and others have shown that the biogenesis of miRs can be regulated post-transcriptionally by RNA-Binding Proteins (RBPs) that binds to their precursor transcripts (Michlewski and Caceres RNA 2019).
We have discovered pathways that regulate biogenesis of miR-7, which is directly involved in Parkinson’s disease (PD) (Michlewski et al. Genes Dev 2013). One of the main causes behind PD is overproduction and aggregation of a protein called alpha-synuclein (alpha-Syn) in the brain cells of affected individuals. Thus, decreasing the levels of alpha-Syn should be beneficial for PD patients. Notably, miR-7 has been shown to target alpha-Syn production and approaches for miR-7 replacement therapies have been put forward.
In this seminar, I will demonstrate how miR-7 is regulated by endogenous RBP - HuR (ELAVL1). I will also present a novel drug discovery platform, based on RNA-Protein Interactions in Eukaryotic Cell Extracts with Confocal Nanoscanning (RP-CONA) to screen for specific compounds interfering with the RNA-protein complexes (Zhu et al., NAR 2021). This new methodology allowed discovering compounds that disrupt RNA/HuR interactions, which in turn decrease alpha-Syn levels, and provide potential leads towards PD therapy.
We will connect via zoom, please use the following link:
Meeting ID: 982 2223 1110