Research Description |
Research in my lab centers around the biology of RNA. In eukaryotic cells, stable RNAs are transcribed with a 3’ extension that is subsequently trimmed from 3’-to-5’, whereas aberrantly processed RNAs are subject to rapid degradation. A conserved 300 – 400 kDa exoribonuclease protein complex, the exosome, plays crucial roles in both the RNA 3’-end formation and turnover processes (Fig. 1). The nuclear exosome is required for the 3’ end formation of 5.8S rRNA, small nuclear and nucleolar RNAs; and involved in the degradation of inefficiently spliced and hyper– or hypo-adenylated pre-mRNAs. The cytoplasmic exosome is required for the degradation of normal mRNAs as well as those containing premature termination codons, lacking termination codons, or bearing AU-rich elements near the 3’ untranslated region. Using X-ray crystallography and biochemical tools, we aim to understand the architecture, working mechanism, and the regulation of this multi-subunit machinery. |
Publications |
R.J. Spanggord, F. Siu, A. Ke, J.A. Doudna (2005), RNA-mediated interaction between the peptide binding and GTPase domains of the signal recognition particle. Nature Structural & Molecular Biology (accepted)
A. Ke and J.A. Doudna (2005), Catalytic strategies of self-cleaving ribozymes: Relics of an RNA world? The RNA World, 3rd Edition. (Book chapter, in print)
A. Ke and J.A. Doudna (2004), Crystallization of RNA and RNA-protein complexes. Methods 34, 408-414.
A. Ke, K. Zhou, F. Ding, J.H.D. Cate, and J.A. Doudna (2004), A conformational switch controls hepatitis delta virus ribozyme catalysis. Nature 429, 201-205 |
