Tien-Hsien Chang

Focus

Yeast RNA helicases involved in nuclear pre-mRNA splicing, mRNA export & translation

Research interests

We are studying the functions of the ubiquitous DExD/H-box proteins, which are often referred to as RNA helicases or RNA unwindases.  These proteins are essential for all RNA-related biological processes such as pre-mRNA splicing, ribosomal biogenesis, mRNA export, translation, and RNA turnover.  Consequently, they are of central importance to the cellular genetic information flow.

Although initially thought to function in a manner similar to that of the DNA helicases, it is now clear that DExD/H-box proteins are likely to function differently.  An emerging hypothesis, on the basis of works done by us and others, is that DExD/H-box proteins function as "RNPases" to "re-configure" various ribonucleoprotein (RNP) complexes transiting the information-flow pathway.  In this view, RNPs are continuously remodelled by DExD/H-box proteins from the time of their birth by transcription and their passage through splicing, export, translation, and their ultimate demise, the RNA turnover.  Thus, in a sense, DExD/H-box proteins may govern the itinerary and the fate of the information packages from cradle to grave.

To illuminate the fascinating roles of these DExD/H-box proteins, we have used budding yeast as a model system.  Yeast provides with us an unparalleled advantage to integrate the powerful tools of molecular genetics, functional genomics, biochemistry, and cell biology.  Last, but not least, we are also exploring the possibility that one of the cellular DExD/H-box proteins is required for hepatitis C virus (HCV) replication, which has so far defied detailed analysis owing to a lack of a suitable tissue culture system.  Studies of this DExD/H-box protein may provide a critical handle to understand how HCV replicates in the cell.

 

Publications

• Kapadia, F., Yang, Z., Pryor, A., Chang, T.-H., and Johnson, L. F. Nuclear localization of poly(A)+ mRNA following siRNA reduction of expresssion of the mammalian RNA helicases UAP56 and URH49. Submitted.
• Burckin, T., Nagel, R., Mandel-Gutfreund, Y., Shiue, L. Clark, T. A. Chong, J.-L., Chang, T.-H., Squazzo, S., Hartzog, G., and Ares. M. Jr. Exploring functional relationships between components of the transcription, splicing, and mRNA export machineries by gene expression phenotype analysis. Nature Struct. Mol. Biol. 12, 175-182.
• Chong,, J.-L., Chuang, R.-Y., Tung, L., and Chang, T.-H. Ded1p, a conserved DExD/H-box translation factor, can promote L-A virus negative-strand RNA synthesis in vitro. Nucl. Acids Res. 32, 2031-2038.
• Pryor, A., Tung, L., Yang, L., Kapadia, F., Chang, T.-H., and Johnson, L. F. Growth-regulated expression and G0-specific turnover of the mRNA that encodes URH49, a mammalian DExD/H-box protein that is highly related to the mRNA export protein UAP56. Nucl. Acids Res. 32, 1857-1865.
• Tseng-Rogenski, S. S.-I, Chong, J.-L., Thomas, C. B., Enomoto, S. Berman, J., and Chang, T.-H. Functional conservation of Dhh1p, a DExD/H-box protein in Saccharomyces cerevisiae. Nucl. Acids Res. 31, 4995-5002.
• Chen, J. Y.-F., Stands, L., Staley, J. P., Jackups, Jr., R. R., Latus, L. J., and Chang, T.-H.. Specific alterations of U1-C protein or U1 small nuclear RNA can eliminate the requirement of Prp28p, an essential DEAD-box splicing factor. Mol. Cell. 7, 227-232.