期刊
RNA
卷 19, 期 1, 页码 17-35出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.034769.112
关键词
Argonaute; microRNA-mediated gene silencing; nuclear export signal; nuclear localization signal; TNRC6A
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
- Cell Innovation Project (MEXT)
- Grants-in-Aid for Scientific Research [21310123, 21115004] Funding Source: KAKEN
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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