Research in my lab focuses on studies of the regulation of mRNA stability in the mammalian cell. Our efforts currently focus on two mechanisms that trigger rapid decay of mRNAs. One pathway is called nonsense-mediated mRNA decay (NMD) by which the mammalian cell recognizes and selectively degrades premature termination codon (PTC)-containing defective transcripts before they generate potentially deleterious truncated proteins. The other pathway is called Staufen1-mediated mRNA decay (SMD) by which the cellular protein Staufen1 binds to the specific mRNAs and thereby recruits mRNA decay machinery at the 3’ untranslated region (3’UTR). We are also examining the basic physiologic importance of NMD and SMD through the identification of several trans-acting factors essential for mRNA degradation. Specific interactions of these factors are being analyzed by genetic and biochemical approaches.
A model illustrating the hyperphosphorylation of Upf1 by SMG1 kinase after PTC recognition, its movement into P bodies, and recruitment of the decapping complex, which are mediated by the serial interactions of hyperphosphorylated Upf1-PNRC2-Dcp1a-Dcp2 (Cho et al., 2009, Molecular Cell).
Model of CBP80/20-dependent translation and eIF4E-dependent translation in mammalian cells (Kim et al., 2009, Genes and Development).
Characterization of molecular mechanism by which non-functional mRNAs containing premature termination codon or cellular mRNAs containing Staufen1 binding site at the 3’UTR are recognized and selectively down-regulated in mammalian cells.
- Understanding of mRNA decay mechanism by NMD and SMD
- Identification of factors essential for NMD and SMD
- Studies on physiological role of NMD and SMD
2007년 이후 대표논문
Hana Cho, Kyoung Mi Kim, Sisu Han, Junho Choe, Seung Gu Park, Sun Shim Choi, and Yoon Ki Kim (2012)
Staufen1-mediated mRNA decay functions in adipogenesis. Molecular Cell, In press
Junho Choe, Hana Cho, Hyung Chul Lee, and Yoon Ki Kim (2010)
microRNA/Argonaute 2 regulates nonsense-mediated messenger RNA decay. EMBO Reports, 11(5):380-386
Kyoung Mi Kim, Hana Cho, Kobong Choi, Jaedong Kim, Bong-Woo Kim, Young-Gyu Ko, Sung Key Jang, and Yoon Ki Kim. (2009)
A new MIF4G domain-containing protein, CTIF, directs nuclear cap-binding protein CBP80/20-dependent translation. Genes and Development, 23(17):2033-2045
Hana Cho, Kyoung Mi Kim, and Yoon Ki Kim (2009)
Human proline-rich nuclear receptor coregulatory protein 2 mediates an interaction between mRNA surveillance machinery and decapping complex. Molecular Cell, 33(1):75-86
Chenguang Gong, Yoon Ki Kim, Collynn F. Woeller, Yalan Tang, and Lynne E. Maquat (2009)
SMD and NMD are competitive pathways that contribute to myogenesis: effects on PAX3 and myogenin mRNAs. Genes and Development, 23(1):54-66
Arneet L. Saltzman, Yoon Ki Kim, Qun Pan, Matthew M. Fagnani, Lynne E. Maquat, and Benjamin J. Blencowe (2008)
Regulation of multiple core spliceosomal proteins by alternative splicing-coupled nonsense-mediated mRNA decay. Mol. Cell. Biol. 28(13):4320-4330
Olaf Isken, Yoon Ki Kim, Nao Hosoda, Greg L. Mayeur, John W.B. Hershey and Lynne E. Maquat (2008)
Upf1 phosphorylation triggers translational repression during nonsense-mediated mRNA decay. Cell 133(2):314-327
Daiki Matsuda, Nao Hosoda, Yoon Ki Kim, and Lynne E. Maquat (2007)
Failsafe nonsense-mediated mRNA decay does not detectably target eIF4E-bound mRNA. Nat. Struct. Mol. Biol. 14(10):974-979
Yoon Ki Kim, Luc Furic, Marc Parisien, Francois Major, Luc DesGroseillers and Lynne E. Maquat. (2007)
Staufen1 Regulates Diverse Classes of Mammalian Transcripts. EMBO J. 26(11):2670-2681
Kwon Tae You, Long Shan Li, Nam-Gyun Kim, Hyun Ju Kang, Kwi Hye Koh, Yong-Joon Chwae, Kyoung Mi Kim, Yoon Ki Kim, Sung Mi Park, Sung Key Jang, and Hoguen Kim (2007)
Selective translational repression of truncated proteins from frameshift mutation-derived mRNAs in tumors. PLOS Biology 5(5):e109