| The La protein was first identified as a major autoantigen in patients suffering from systemic lupus erythematosus and Sjogren's syndrome. La binds to the 3' ends of many newly synthesized noncoding RNA precursors and can influence the stability, processing pathway and structure of these RNAs. Although the RNA 3' end binding function of the La protein is ascribed to the N-terminal La and RNA recognition motif (RRM), the ability of the La protein to influence the structure of RNAs is not well understood. In this thesis, I examine the functional role of the disordered C-terminus in Saccharomyces cerevisiae La homolog, Lhp1p. I demonstrated that the C-terminus does not affect the ability of Lhp1p to bind to the 3' ends of pre-tRNAs or a U4 snRNA, and is not required for the role of La in influencing the pathway of pre-tRNA maturation in vivo. The C-terminus is required to stabilize 3' extended forms of the U4 snRNA and the U3 snoRNA and is necessary for efficient charging of a mutant tRNA. In the absence of a RNA ligand, the C-terminus is protease sensitive, but becomes protease resistant when bound to a structured RNA ligand, suggesting the region may be gaining structured order upon ligand binding. Intrinsically disordered protein regions are found in many RNA binding proteins that can bind multiple ligands and influence RNA structure. I speculate that conformational flexibility of the La protein's C-terminus is responsible for the promiscuity in binding that allows for the stabilization of a diverse repertoire of RNA substrates. |
