Some ELAV-like proteins, discovered first in Drosophila, appear to be involved in the development and maintenance of neurons. In the Drosophila ELAV mutant, the nervous system is dysfunctional while human ELAV-like proteins are target antigens in paraneoplastic sensory neuropathy, autoimmune neural degeneration associated with small cell lung cancer. Four human ELAV-like proteins, Hu proteins, have been identified. HuR is ubiquitously expressed while HelN1, HuC, and HuD are expressed in neurons. The Hu proteins contain three highly conserved RNA binding domains belonging to the RRM (RNA recognition motif) superfamily. The first two RRMs are in tandem and have been reported to bind to the AU-rich elements of certain mRNAs and the third RRM has been shown to bind to long poly-A tails. Recent studies on HuR suggest that Hu proteins may stabilize the mRNAs to which they bind. Although structures of the RRMs from ELAV-like proteins have not been determined, x-ray crystallographic and NMR studies have shown the overall fold of RRMs from other proteins and how they bind to RNA. The goal of this project is to determine the three-dimensional structures of Hu protein RRMs bound to RNA elements in order to analyze the protein-RNA interactions, provide insight into how recognition of different RNA sequences is achieved by a common protein fold, and understand how the protein-RNA interactions may stabilize or destabilize the mRNA. Several proteins containing different RRMs are currently being expressed in E. coli and purified for crystallographic studies.
| 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) Multiple modes of RNA recognition by zinc finger proteins. Curr Opin Struct Biol 15:367-73 |
| Hall, Traci M Tanaka (2005) Structure and function of argonaute proteins. Structure 13:1403-8 |
| 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 |
