Structure-Function Investigation of Specific tsRNAs
The long-term goal of the Schaefer group is to understand how specific RNA modifications influence the re-programming of cellular processes during stress conditions. Stress-induced production of tRNA-derived small RNAs (tsRNAs) is an evolutionary conserved phenomenon. However, the mechanistic underpinnings as to how exactly specific tsRNAs function remain unclear.
Within this SFB and in collaboration with , the Schaefer group aims at determining the structure and half-life of specific tsRNA and at identifying proteins that associated with these tsRNAs. To do so, the Schaefer group will employ biochemical approaches and purify specific tsRNAs from mouse embryonic fibroblasts carrying viable mutations in two conserved (cytosine-5) tRNA methyltransferases (Dnmt2/TRDMT1 and NSUN2). Purified tsRNAs carrying different RNA modification patterns will be used for structural probing (with Micura, Rossmanith & Hofacker), for re-introduction experiments to study localization and turnover of specific tsRNAs (with Ameres), and for protein binding assays to identify tsRNA-interacting proteins (with Martinez & Vilardo).