The origins of human diseases, such as cancer, can be generally attributed to loss-of-function of important genes (tumor suppressor genes) and/or gain-of-function of pathological genes (oncogenes). My lab is interested in understanding how cells use small RNAs to silence gene expression and how to harness RNAi to treat human diseases by shutting down expression of pathological genes.
RNAi is a post-transcriptional gene silencing mechanism mediated by 21- to 25- nucleotide small interfering RNAs (siRNAs) and microRNAs (miRNAs). The three core components of RNAi are: Dicer, Ago, dsRBP. Dicer, a multidomain RNase III enzyme, processes long double-stranded (ds)RNA into siRNA, and pre-miRNA into miRNA. Argonaute (Ago), guided by a siRNA or miRNA, directs sequence-specific cleavage and translational repression of cognate mRNA. DsRNA-binding protein (dsRBP), such as R2D2 in flies, facilitates transfer of siRNA from Dicer to Ago to form the RNA-induced silencing (RISC) complex.
We have previously identified that Dicer-1/R3D1 and Dicer-2/R2D2 generate miRNAs and siRNAs, respectively, in Drosophila. Reconstitution studies establish that Dicer-1 and Dicer-2 show different substrate specificities and ATP requirements. R2D2 does not regulate siRNA production. Rather, R2D2 and Dcr-2 coordinately bind siRNA to promote assembly of the siRISC complexes. On the other hand, R3D1 enhances miRNA production and is required for Drosophila development. Our studies demonstrate that R3D1 plays a critical role in self-renewal of germline stem cells (GSC). Future directions: 1) In vitro reconstitution of RNAi; 2) Identify novel components and regulators of RNAi; 3) Regulatory mechanisms of the RNAi pathway. 4) Mechanisms of translational repression.
RESEARCH INTERESTS
Biochemical mechanism of RNA interference
Regulation of RNA interference
MicroRNA-mediated translational repression
Drosophila germline stem cells
RECENT PUBLICATIONS
F. Jiang, X. Ye, X. Liu, L. Fincher, D. McKearin, Q. Liu, "Dicer-1 and R3D1-L catalyze miRNA maturation in Drosophila." Genes Dev., 19:1674-1679, 2005
J. Park*, X. Liu*, T. Strauss, D. McKearin, and Q. Liu, "The miRNA pathway intrinsically controls self-renewal of Drosophila germline stem cells." Curr. Biol., 17:533-538, 2007
X. Ye, P. Zain, and Q. Liu, "The functional anatomy of Drosophiila microRNA-generating enzyme" J. Biol. Chem., 282 (39):28373-28378, July 2007
Z. Paroo, X. Ye, S. Chen, and Q. Liu, "Phosphorylation of the human micro-RNA generating complex mediates MAPK/Erk signaling" Cell, In press October 2009
Y. Liu, X. Ye, F. Jiang, C. Liang, D. Chen, P. Jun, L.N. Kinch, N.V. Grishin, Q. Liu, "C3PO, an endoribonuclease that promotes RNAi by facilitating RISC activation" Science, 325:750-753, August 2009
SIGNIFICANT PUBLICATIONS
Q. Liu, M. Z. Li, D. Liebham, D. Cortez, S. J. Elledge, "The univector plasmid-fusion system, a method for rapid construction of recombinant DNA without restriction enzymes." Curr. Biol., 8:1300-1309, 1998
Q. Liu, S. Guntuku, X. Cui, S. Matsuoka, D. Cortez, K. Tamai, G. Luo, S. Carattini-Rivera, F. Demayo, A. Bradley, L.A. Donehower, and S.J. Elledge, "Chk1 is an essential kinase that is regulated by Atr and required for the G2/M DNA damage checkpoint." Genes Dev., 14:1448-1459, 2000
Q. Liu, T. A. Rand, S. Kalidas, F. Du, H. Kim, D.P. Smith, X. Wang, "R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway." Science, 301:1921-1925, 2003
F. Jiang, X. Ye, X. Liu, L. Fincher, D. McKearin, Q. Liu, "Dicer-1 and R3D1-L catalyze miRNA maturation in Drosophila" Genes Dev., 19:1674-1679, 2005
J. Park, X. Liu, T. Strauss, F. Jiang, Y. Liu, D. McKearin, and Q. Liu, "The miRNA pathway intrinsically controls self-renewal of Drosophila germline stem cells." Curr. Biol., 17:533?538, 2007
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