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Molecular and Cellular Biology, November 2009, p. 5789-5799, Vol. 29, No. 21
0270-7306/09/$08.00+0     doi:10.1128/MCB.00653-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Human UPF1 Participates in Small RNA-Induced mRNA Downregulation{triangledown} ,{dagger}

Hua Jin,{ddagger} Mi Ra Suh,{ddagger} Jinju Han, Kyu-Hyeon Yeom, Yoontae Lee, Inha Heo, Minju Ha, Seogang Hyun, and V. Narry Kim*

School of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea

Received 20 May 2009/ Returned for modification 23 June 2009/ Accepted 17 August 2009

MicroRNAs (miRNAs) are endogenous antisense regulators that trigger endonucleolytic mRNA cleavage, translational repression, and/or mRNA decay. miRNA-mediated gene regulation is important for numerous biological pathways, yet the underlying mechanisms are still under rigorous investigation. Here we identify human UPF1 (hUPF1) as a protein that contributes to RNA silencing. When hUPF1 is knocked down, miRNA targets are upregulated. The depletion of hUPF1 also increases the off-target messages of small interfering RNAs (siRNAs), which are imperfectly complementary to transfected siRNAs. Conversely, when overexpressed, wild-type hUPF1 downregulates miRNA targets. The helicase domain mutant of hUPF1 fails to suppress miRNA targets. hUPF1 interacts with human Argonaute 1 (hAGO1) and hAGO2 and colocalizes with hAGO1 and hAGO2 in processing bodies, which are known to be the sites for translational repression and mRNA destruction. We further find that the amounts of target messages bound to hAGO2 are reduced when hUPF1 is depleted. Our data thus suggest that hUPF1 may participate in RNA silencing by facilitating the binding of the RNA-induced silencing complex to the target and by accelerating the decay of the mRNA.

* Corresponding author. Mailing address: School of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Phone: 82-2-880-9120. Fax: 82-2-887-0244. E-mail: narrykim{at}snu.ac.kr

{triangledown} Published ahead of print on 24 August 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} These authors contributed equally to this study.

Molecular and Cellular Biology, November 2009, p. 5789-5799, Vol. 29, No. 21
0270-7306/09/$08.00+0     doi:10.1128/MCB.00653-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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