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MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies


Small RNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs) can silence target genes through several different effector mechanisms1. Whereas siRNA-directed mRNA cleavage is increasingly understood, the mechanisms by which miRNAs repress protein synthesis are obscure. Recent studies have revealed the existence of specific cytoplasmic foci, referred to herein as processing bodies (P-bodies), which contain untranslated mRNAs and can serve as sites of mRNA degradation2,3,4,5,6,7. Here we demonstrate that Argonaute proteins — the signature components of the RNA interference (RNAi) effector complex, RISC — localize to mammalian P-bodies. Moreover, reporter mRNAs that are targeted for translational repression by endogenous or exogenous miRNAs become concentrated in P-bodies in a miRNA-dependent manner. These results provide a link between miRNA function and mammalian P-bodies and suggest that translation repression by RISC delivers mRNAs to P-bodies, either as a cause or as a consequence of inhibiting protein synthesis.

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Figure 1: Argonaute proteins localize to mammalian P-bodies.
Figure 2: Argonaute proteins bind components of mammalian P-bodies.
Figure 3: Accumulation of Argonaute proteins in P-bodies requires an intact siRNA-binding domain.
Figure 4: miRNA-dependent localization of target mRNAs to mammalian P-bodies.

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We thank members of the Hannon laboratory for helpful discussions, S. Hearn from the CSHL microscopy shared resource for assistance, and S. Janicki (CSHL), J. Lykke-Andersen (University of Colorado) and T. Achsel (University of Wurzburg) for reagents. J.L. is supported by a Special Fellow award from the Leukemia and Lymphoma Society. This work was supported by grants from the NIH (to G.J.H. and R.P.). R.P. is an investigator at the Howard Hughes Medical Institute.

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Correspondence to Gregory J. Hannon or Roy Parker.

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Liu, J., Valencia-Sanchez, M., Hannon, G. et al. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol 7, 719–723 (2005).

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