Cited by 188MicroRNA in disease regulationRNA Interference and Gene DeliveryRNA Research and Splicing

Human TNRC6A is an Argonaute-navigator protein for microRNA-mediated gene silencing in the nucleus

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Nishi, Kenji, Nishi, Ai, Nagasawa, Tatsuya, Ui-Tei, Kumiko·2013·RNA

Abstract

GW182 family proteins play important roles in microRNA (miRNA)-mediated gene silencing. They interact with Argonaute (Ago) proteins and localize in processing bodies, which are cytoplasmic foci involved in mRNA degradation and storage. Here, we demonstrated that human GW182 paralog, TNRC6A, is a nuclear-cytoplasmic shuttling protein, and its subcellular localization is conducted by a nuclear export signal (NES) and a nuclear localization signal (NLS) identified in this study. TNRC6A with mutations in its NES region was predominantly localized in the nucleus in an Ago-independent manner. However, it was found that TNRC6A could bring Ago protein into the nucleus via its Ago-interacting motif(s). Furthermore, miRNAs were also colocalized with nuclear TNRC6A-Ago and exhibited gene silencing activity. These results proposed the possibility that TNRC6A plays an important role in navigating Ago protein into the nucleus to lead miRNA-mediated gene silencing.

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Crossref · 10.1261/rna.034769.112

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  • Low molecular weight miRISC can interact with mRNAs within the nucleus and induce nuclear mRNA degradation.

    “It has been reported that low molecular weight miRISC can interact with mRNAs within the nucleus and induce nuclear mRNA degradation, although the mechanism behind this is unclear (59, 61, 63).”
  • Human AGO2 shuttles between the nucleus and cytoplasm via its interaction with TNRC6A through Importin-8 or Exportin-1.

    “Through Importin-8 or Exportin-1, human AGO2 shuttles between the nucleus and cytoplasm via its interaction with TNRC6A (a GW182 family protein) which contains a nuclear localization and export signal (59).”

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Authors
Nishi, K., Nishi, A., Nagasawa, T., & Ui-Tei, K.
Affiliations
The University of Tokyo (JP)
Venue
RNA
Published
2012-11-13
Volume
19
Issue
1
Pages
17-35
ISSN
  • 1355-8382 (ISSN-L)
  • 1469-9001
OpenAlex
W2144203440
Cited by
188
References
62
Citations by year
2026: 12 · 2025: 15 · 2024: 9 · 2023: 22 · 2022: 23 · 2021: 14 · 2020: 10 · 2019: 13 · 2018: 14 · 2017: 18 · 2016: 7 · 2015: 11 · 2014: 15 · 2013: 5
FWCI
3.28
Type
journal article
Language
en
Open access
Locations
  • RNA (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology
  • Japan Society for the Promotion of Science (21115004, 23651200, 21310123)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
TNRC6A, Argonaute proteins, microRNA silencing, nucleocytoplasmic shuttling, nuclear export signal, nuclear localization signal, RNA silencing
MeSH terms
Autoantigens, Cell Nucleus, HeLa Cells, Humans, Mutation, RNA-Binding Proteins, Nuclear Localization Signals, Amino Acid Motifs, Gene Silencing, Nucleocytoplasmic Transport Proteins, MicroRNAs, Nuclear Export Signals, Argonaute Proteins

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