鄭淑珍 Soo-Chen Cheng

Molecular Mechanism of Pre-mRNA Splicing

I was trained as a biochemist for graduate research at Duke University, studying protein-DNA interactions with Paul Modrich. I worked on pre-mRNA splicing as a postdoc with John Abelson at Caltech, where I was involved in developing a yeast in vitro splicing system, and established a preliminary spliceosome assembly pathway. I continued to study yeast splicing after establishing my own laboratory at the Academia Sinica.

My research work focused on the identification and characterization of protein splicing factors, aiming to understand their functional roles in the splicing process, and to uncover detailed mechanisms of the splicing reaction. We have characterized several protein splicing factors, revealing their functions in spliceosome assembly, activation and disassembly, as well as in catalytic steps. We also unraveled the mystery of the ATP requirement for both catalytic steps, showing ATP-dependent remodeling of the spliceosome mediated by DEAH-box proteins, Prp2 and Prp16, for positioning and repositioning of splice sites. We have further elucidated dynamic properties of the spliceosome for its chemical flexibility and for protein-RNA interactions. We are among the leading groups in understanding the molecular mechanism of the pre-mRNA splicing reaction. In addition, while several DExD/H-box proteins have previously been implicated in proofreading splice sites to ensure splicing fidelity from genetic studies, we have recently uncovered a contradictory role of Prp16 and Prp22 in promoting selection of aberrant splice sites, overriding its proofreading function. Most recently, we have formulated a new model for how mRNA is released from the spliceosome, in which Prp22-mediated ATP hydrolysis induces a conformational change in Prp8 that creates an exit tunnel.