Importin-β facilitates nuclear import of human GW proteins and balances cytoplasmic gene silencing protein levels

Daniel Schraivogel, Susann Gaby Schindler, Johannes Danner, Elisabeth Kremmer, Janina Pfaff, Stefan Hannus, Reinhard Depping, Gunter Meister*

*Corresponding author for this work
29 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) guide Argonaute (Ago) proteins to distinct target mRNAs leading to translational repression and mRNA decay. Ago proteins interact with a member of the GW protein family, referred to as TNRC6A-C in mammals, which coordinate downstream gene-silencing processes. The cytoplasmic functions of TNRC6 and Ago proteins are reasonably well established. Both protein families are found in the nucleus as well. Their detailed nuclear functions, however, remain elusive. Furthermore, it is not clear which import routes Ago and TNRC6 proteins take into the nucleus. Using different nuclear transport assays, we find that Ago as well as TNRC6 proteins shuttle between the cytoplasm and the nucleus. While import receptors might function redundantly to transport Ago2, we demonstrate that TNRC6 proteins are imported by the Importin-β pathway. Finally, we show that nuclear localization of both Ago2 and TNRC6 proteins can depend on each other suggesting actively balanced cytoplasmic Ago-TNRC6 levels.

Original languageEnglish
JournalNucleic Acids Research
Volume43
Issue number15
Pages (from-to)7447-7461
Number of pages15
ISSN0305-1048
DOIs
Publication statusPublished - 01.07.2015

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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