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Molecular and Cellular Biology, June 2007, p. 3995-4005, Vol. 27, No. 11
0270-7306/07/$08.00+0     doi:10.1128/MCB.00186-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A Double-Stranded-RNA Response Program Important for RNA Interference Efficiency

Swati Choudhary,^1, Heng-Chi Lee,^1, Mekhala Maiti,^1, Qun He,^1, Ping Cheng,^1, Qinghua Liu,² and Yi Liu^1*

Department of Physiology,¹ Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390²

Received 31 January 2007/ Returned for modification 6 March 2007/ Accepted 13 March 2007

When recognized by the RNA interference (RNAi) pathway, double-stranded RNA (dsRNA) produced in eukaryotic cells results in posttranscriptional gene silencing. In addition, dsRNA can trigger the interferon response as part of the immune response in vertebrates. In this study, we show that dsRNA, but not short interfering RNA (siRNA), induces the expression of qde-2 (an Argonaute gene) and dcl-2 (a Dicer gene), two central components of the RNAi pathway in the filamentous fungus Neurospora crassa. The induction of QDE-2 by dsRNA is required for normal gene silencing, indicating that this is a regulatory mechanism that allows the optimal function of the RNAi pathway. In addition, we demonstrate that Dicer proteins (DCLs) regulate QDE-2 posttranscriptionally, suggesting a role for DCLs or siRNA in QDE-2 accumulation. Finally, a genome-wide search revealed that additional RNAi components and homologs of antiviral and interferon-stimulated genes are also dsRNA-activated genes in Neurospora. Together, our results suggest that the activation of the RNAi components is part of a broad ancient host defense response against viral and transposon infections.

Published ahead of print on 19 March 2007.

S.C., H.-C.L., and M.M. contributed equally to this study.

Present address: State Key Laboratory for Agro-Biotechnology, College of Biological Sciences, Chinese Agricultural University, Beijing 100094, People's Republic of China.

Present address: Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065.

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