Importin 8 Regulates the Transport of Mature MicroRNAs into the Cell Nucleus
| Autor: | Ke Zen, Dong Wang, Limin Li, Chen-Yu Zhang, Yao Wei |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
alpha Karyopherins
Active Transport Cell Nucleus Importin Biology Importin 8 Biochemistry Cell Line Mice microRNA medicine Animals Gene Regulatory Networks RNA Small Interfering Molecular Biology Cytoskeleton Karyopherin Cell Nucleus chemistry.chemical_classification Alpha Karyopherins Cell Biology Argonaute Molecular biology Cell biology MicroRNAs Cell nucleus medicine.anatomical_structure Microscopy Fluorescence chemistry Argonaute Proteins Nuclear transport Protein Binding Reports |
| Zdroj: | Journal of Biological Chemistry. 289:10270-10275 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.c113.541417 |
| Popis: | Mature microRNAs (miRNAs), ∼ 22-nucleotide noncoding RNAs regulating target gene expression at the post-transcriptional level, have been recently shown to be transported into the nucleus where they modulate the biogenesis of other miRNAs or their own expression. However, the mechanism that governs the transport of mature miRNAs from cytoplasm to nucleus remains unknown. Here, we report that importin 8 (IPO8), a member of the karyopherin β (also named the protein import receptor importin β) family, plays a critical role in mediating the cytoplasm-to-nucleus transport of mature miRNAs. Specifically knocking down IPO8 but not other karyopherin β family proteins via siRNA significantly decreases the nuclear transport of various known nucleus-enriched miRNAs without affecting their total cellular levels. IPO8-mediated nuclear transport of mature miRNAs is also dependent on the association of IPO8 with the Argonaute 2 (Ago2) complex. Cross-immunoprecipitation and Western blot analysis show that IPO8 is physically associated with Ago2. Knocking down IPO8 via siRNA markedly decreases the nuclear transport of Ago2 but does not affect the total cellular Ago2 level. Furthermore, dissociating the binding of miRNAs with Ago2 by trypaflavine strongly reduces the IPO8-mediated nuclear transport of miRNAs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|