Human TNRC6A is an Argonaute-navigator protein for microRNA-mediated gene silencing in the nucleus
Open accessAbstract
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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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).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [59]
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).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [59]
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Self-citation
- Authors
- Nishi, K., Nishi, A., Nagasawa, T., & Ui-Tei, K.
- Affiliations
- The University of Tokyo (JP)
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-11-13
- Volume
- 19
- Issue
- 1
- Pages
- 17-35
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- PMC
- PMC3527724
- 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
- bronze
- doi.org
- 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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