John L. Wang

Research Interests

The work described below is carried out in close collaboration with the laboratory of Dr. Ron Patterson (Department of Microbiology and Molecular Genetics).

The research interests of our laboratories are focused on two carbohydrate-binding proteins, galectin-1 and galectin-3. The galectins comprise a family of galactose-binding proteins that share characteristic amino acid sequences in the carbohydrate recognition domain of the polypeptides. Our interest in this system stemmed from the observation that galectin-3 was found as a ribonucleoprotein complex in the nucleus. Using nuclear extracts derived from HeLa cells, capable of carrying out splicing of pre-mRNA in a cell-free assay, depletion and reconstitution experiments demonstrated that galectins-1 and -3 are splicing factors. More recently, we have documented that galectins-1 and -3 both independently bind to a protein designated Gemin4. The significance of this finding lies in the fact that other investigators had shown that Gemin4 is one component of a macromolecular complex, the SMN complex, that plays important roles in the biogenesis, delivery, and regeneration of small nuclear ribonucleoprotein particles (snRNPs) for spliceosome assembly. On the basis of these and other observations, the immediate objectives of our research include:

(a) to delineate and characterize the components and interactions of the ribonucleoprotein complex on which galectins-1 and -3 have been found;

(b) to define the step(s) during which galectins-1 and -3 participate in splicing;

(c) to test, by site-directed mutagenesis, whether carbohydrate-binding is required for the role of; galectins in the splicing reaction;and

(d) to study the nucleo-cytoplasmic shuttling properties of galectin-3, in terms of import and export signals and in terms of a possible role in mRNA transport.

Recent Publications

Voss, P.G., Haudek, K.C., Patterson, R.J., and Wang, J.L. (2011) Inhibition of cell-free splicing by saccharides that bind galectins and SR proteins. J. Carbohydrate Chemistry, in press. Link to pdf

Haudek, K.C., Patterson, R.J., and Wang, J.L. (2010) SR proteins and galectins: what’s in a name? Glycobiology, 20: 1199-1207. Link to pdf

Haudek, K.C., Spronk, K.J., Voss, P.G., Patterson, R.J., Wang, J.L. and Arnoys, E.J. (2010) Dynamics of galectin-3 in the nucleus and cytoplasm. Biochim. Biophys. Acta, 1800: 181-189. Link to pdf

Haudek, K.C., Voss, P.G., Locascio, L.E., Wang, J.L. and Patterson, R.J. (2009) A mechanism for incorporation of galectin-3 into the spliceosome through its association with U1 snRNP. Biochemistry. 48, 7705–7712. Link to pdf

Wang, J.L., Haudek, K.C., Voss, P.G. and Patterson, R.J. (2008) Nuclear and cytoplasmic localization of galectin-1 and galectin-3 and their roles in pre-mRNA splicing, in Galectins (A.A. Klyosov, Z.J. Witczak, and D. Platt, eds.), John Wiley & Sons, pp. 87-95. Link to pdf

Voss, P.G., Gray, R.M., Dickey, S.W., Wang, W., Park, J.W., Kasai, K., Hirabayashi, J., Patterson, R.J., and Wang, J.L. (2008) Dissociation of the carbohydrate-binding and splicing activities of galectin-1, Arch. Biochem. Biophys., 478: 18-25. Link to pdf

Gray, R.M., Davis, M.J., Ruby, K.M., Voss, P.G., Patterson, R.J., and Wang, J.L. (2008) Distinct effects on splicing of two monoclonal antibodies directed against the amino-terminal domain of galectin-3, Arch. Biochem. Biophys. 475: 100-108. Link to pdf

Arnoys, E.A. and Wang, J.L. (2007) Dual localization: proteins in extracellular and intracellular compartments.  Acta Histochemica 109: 89-110. Link to pdf