Disection of Target-Directed MicroRNA Degradation mechanism

SALGADO FAUSTINA; FUCHS WIGHTMAN FEDERICO; DE LA MATA MANUEL

Buenos Aires

Conferencia; FRONTIERS IN BIOSCIENCE 4; 2023

IBioBA, CONICET-MPSP, Buenos Aires

MicroRNAs (miRNAs) are small non-coding RNAs whose function is to silence messenger RNAs (mRNAs) inmany essential cell processes. Their biogenesis and function have been studied in depth, but the mechanismsof their degradation are still not well understood. The best-known miRNA degradation mechanism, calledTDMD (target RNA-directed miRNA degradation), reverses the logic by which miRNAs induce the degradationof their specific RNA targets. During TDMD, certain RNAs containing high-affinity sites for specific miRNAstrigger the degradation of these miRNAs. According to recent findings, the interaction between aTDMD-inducing target RNA and a specific miRNA loaded on an Argonaut protein (AGO) generates aconformational change in the latter, leading to its polyubiquitination and subsequent degradation. Thus,specific miRNAs become unprotected and susceptible to degradation by general nucleases. In this project, weaim to elucidate how the TDMD machinery is recruited to the miRNA-induced silencing complex (miRISC), ofwhich AGO is one of its central components, and how its activity is regulated in the context of TDMD.