Human antigen (Hu) proteins HuB, HuC, HuD, and HuR are a family of RNA-binding protein that stabilize mRNA by binding to AU-rich elements (ARE) in the 3’UTR. HuR is universally expressed in human cells, and stabilizes many tumor-related genes such as bcl-2. HuR is upregulated in many cancer cell types involved in breast and colon cancer. EXC-7 is the sole homologue of the Hu proteins in C. elegans. EXC-7 maintains the single-cell tubular canals of the excretory cell by stabilizing sma-1 mRNA, encoding βH-spectrin. Mutants in exc-7 exhibit small fluid-filled cysts throughout shortened excretory canals, as well as a misshapen tailspike. Both EXC-7 and HuR contain 3 RNA-recognition motifs (RRMs), with a region between the 2nd and 3rd RRM that appears to be needed for intracellular transport. We are investigating the functional equivalence of these proteins, by determining whether human HuR can functionally replace EXC-7 in C. elegans. If so, then C. elegans could be developed as a model for studying HuR in vivo, especially for screens for chemicals that interfere with HuR function, using excretory canal phenotype as a measure of HuR activity. I have injected the hur coding region driven by various promoters to express HuR within the excretory canals. HuR cDNA appears to rescue partially both the length and diameter of the excretory canal lumen in exc-7 mutants. Modification of the structure of the injected HuR gene showed better rescue effects. We will further modify the structure of HuR and seek solutions to fully rescue canal defects, and are making worm/human chimeric proteins to investigate domain activity of these proteins and study the binding partners, the mRNA targets of EXC-7.