The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Ago–TNRC6 triggers microRNA-mediated decay by promoting two deadenylation steps
Open accessAbstract
MicroRNAs (miRNAs) silence the expression of their mRNA targets mainly by promoting mRNA decay. The mechanism, kinetics and participating enzymes for miRNA-mediated decay in mammalian cells remain largely unclear. Combining the approaches of transcriptional pulsing, RNA tethering, overexpression of dominant-negative mutants, and siRNA-mediated gene knockdown, we show that let-7 miRNA-induced silencing complexes (miRISCs), which contain the proteins Argonaute (Ago) and TNRC6 (also known as GW182), trigger very rapid mRNA decay by inducing accelerated biphasic deadenylation mediated by Pan2–Pan3 and Ccr4–Caf1 deadenylase complexes followed by Dcp1–Dcp2 complex–directed decapping in mammalian cells. When tethered to mRNAs, all four human Ago proteins and TNRC6C are each able to recapitulate the two deadenylation steps. Two conserved human Ago2 phenylalanines (Phe470 and Phe505) are critical for recruiting TNRC6 to promote deadenylation. These findings indicate that promotion of biphasic deadenylation to trigger mRNA decay is an intrinsic property of miRISCs.
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Cites
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BackgroundAU-rich elements: characterization and importance in mRNA degradation
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Self-citationZebrafish MiR-430 Promotes Deadenylation and Clearance of Maternal mRNAs
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A Mechanism for Translationally Coupled mRNA Turnover
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Regulation of microRNA function in animals
Gebert, L. F. R., & MacRae, I. J. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0045-7 · Cited by 2,284
Towards a molecular understanding of microRNA-mediated gene silencing
Jonas, S., & Izaurralde, E. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3965 · Cited by 1,872
MicroRNAs in Development and Disease
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The Functions of MicroRNAs: mRNA Decay and Translational Repression
Iwakawa, H.-O., & Tomari, Y. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.07.011 · Cited by 732
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Metadata
- Authors
- Chen, C.-Y. A., Zheng, D., Xia, Z., & Shyu, A.-B.
- Venue
- Nature Structural & Molecular Biology
- Published
- 2009-10-18
- Volume
- 16
- Issue
- 11
- Pages
- 1160-1166
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2004864449
- Cited by
- 196
- References
- 6
- FWCI
- 6.22
- Type
- journal article
- Language
- en
- Open access
- green
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- Chen, C.-Y. A., Zheng, D., Xia, Z., & Shyu, A.-B. (2009). Ago–TNRC6 triggers microRNA-mediated decay by promoting two deadenylation steps. Nature Structural & Molecular Biology. https://doi.org/10.1038/nsmb.1709
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