Structure of the Nuclear Factor ALY:  Insights into Post-Transcriptional Regulatory and mRNA Nuclear Export Processes

ALY is a ubiquitously expressed nuclear protein which interacts with proteins such as TAP that are involved in export of mRNA from the nucleus to the cytoplasm, as well as with proteins that bind the T cell receptor α gene enhancer. ALY has also been shown to bind mRNA and to co-localize in the nucleus with components of a multiprotein postsplicing complex that is deposited 20−24 nucleotides upstream of exon−exon junctions. ALY has a conserved RNA binding domain (RBD) flanked by Gly-Arg rich N-terminal and C-terminal sequences. We determined the solution structure of the RBD homology region in ALY by nuclear magnetic resonance methods. The RBD motif in ALY has a characteristic β1α1β2−β3α2β4 fold, consisting of a β sheet composed of four antiparallel β strands and two α helices that pack on one face of the β sheet. As in other RBD structures, the β sheet has an exposed face with hydrophobic and charged residues that could modulate interactions with other molecules. The loop that connects β strands 2 and 3 is in intermediate motion in the NMR time scale, which is also characteristic of other RBDs. This loop presents side chains close to the exposed surface of the β sheet and is a primary candidate site for intermolecular interactions. The structure of the conserved RBD of ALY provides insight into the nature of interactions involving this multifunctional protein.