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Weinmann, L.* ; Höck, J.* ; Ivacevic, T.* ; Ohrt, T.* ; Mütze, J.* ; Schwille, P.* ; Kremmer, E. ; Benes, V.* ; Urlaub, H.* ; Meister, G.*

Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs.

Cell 136, 496-507 (2009)

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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

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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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