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Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs.
Cell 136, 496-507 (2009)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
microrna-dependent localization; human-cells; translation initiation; caenorhabditis-elegans; passenger-strand; mammalian-cells; piwi proteins; in-vitro; mirnas; complexes
ISSN (print) / ISBN
0092-8674
e-ISSN
1097-4172
Zeitschrift
Cell
Quellenangaben
Band: 136,
Heft: 3,
Seiten: 496-507
Verlag
Cell Press
Verlagsort
Cambridge, Mass.
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Molecular Immunology (IMI)