Post-transcriptional regulation of messenger RNA (mRNA) stability and translation are important control points for gene expression. The overall goal of this project is to generate and utilize structural information to enhance our understanding of these processes. We are studying the post-transcriptional regulation by Puf family proteins. This family of proteins are found in organisms from humans to yeast and contain a conserved RNA-binding domain, the Pumilio-homology domain (PUM-HD). Several family members have been shown to regulate the stability or repress the translation of their target mRNAs. We have determined the crystal structure of the PUM-HD from the human Pumilio1 protein in complex with a high-affinity RNA ligand. The crescent-shaped molecule binds RNA on the concave surface while the outer surface interacts with proteins such as Nanos and Brain Tumor. The PUM-HD contains eight approximately 36 amino-acid sequence repeats that correspond to eight structural repeats containing three alpha helices. In the structure of the protein-RNA complex, each repeat binds to one RNA base in a modular fashion using three amino acid side chains from conserved positions. Based on this modular binding mode, we have designed a site-directed mutant protein and demonstrated that it has altered RNA sequence specificity.
| Cheong, Cheom-Gil; Hall, Traci M Tanaka (2006) Engineering RNA sequence specificity of Pumilio repeats. Proc Natl Acad Sci U S A 103:13635-9 |
| Hall, Traci M Tanaka (2005) Structure and function of argonaute proteins. Structure 13:1403-8 |
| Hall, Traci M Tanaka (2005) Multiple modes of RNA recognition by zinc finger proteins. Curr Opin Struct Biol 15:367-73 |
| Hall, Traci M Tanaka (2003) SAM breaks its stereotype. Nat Struct Biol 10:677-9 |
| Vargason, Jeffrey M; Szittya, Gyorgy; Burgyan, Jozsef et al. (2003) Size selective recognition of siRNA by an RNA silencing suppressor. Cell 115:799-811 |
| Hall, Traci M Tanaka (2002) Poly(A) tail synthesis and regulation: recent structural insights. Curr Opin Struct Biol 12:82-8 |
| Wang, X; Zamore, P D; Hall, T M (2001) Crystal structure of a Pumilio homology domain. Mol Cell 7:855-65 |
| Wang, X; Tanaka Hall, T M (2001) Structural basis for recognition of AU-rich element RNA by the HuD protein. Nat Struct Biol 8:141-5 |
