Journal
CELL
Volume 136, Issue 3, Pages 496-507Publisher
CELL PRESS
DOI: 10.1016/j.cell.2008.12.023
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Funding
- Max Planck Society
- Deutsche Forschungsgemeinschaft [Me2064/2-1]
- European Union [LSHG-CT-2006-037900]
- Deutsche Volkswagenstiftung [I/79308]
- Boehringer Ingelheim Fonds
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Small regulatory RNAs including small interfering RNAs (siRNAs) and microRNAs ( miRNAs) guide Argonaute ( Ago) proteins to specific target RNAs leading to mRNA destabilization or translational repression. Here, we report the identification of Importin 8 (Imp8) as a component of miRNA-guided regulatory pathways. We show that Imp8 interacts with Ago proteins and localizes to cytoplasmic processing bodies ( P bodies), structures involved in RNA metabolism. Furthermore, we detect Ago2 in the nucleus of HeLa cells, and knockdown of Imp8 reduces the nuclear Ago2 pool. Using immunoprecipitations of Ago2-associated mRNAs followed by microarray analysis, we further demonstrate that Imp8 is required for the recruitment of Ago protein complexes to a large set of Ago2-associated target mRNAs, allowing for efficient and specific gene silencing. Therefore, we provide evidence that Imp8 is required for cytoplasmic miRNA-guided gene silencing and affects nuclear localization of Ago proteins.
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