Cited by 207RNA Interference and Gene DeliveryRNA Research and SplicingRNA regulation and disease

Human Argonaute 2 Has diverse reaction pathways on Target RNAs

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Jo, Myung Hyun, Shin, Soochul, Jung, Seung-Ryoung, Kim, Eunji, Song, Ji-Joon, Hohng, Sungchul·2015·Molecular Cell

Abstract

Argonaute is a key enzyme of various RNA silencing pathways. We use single-molecule fluorescence measurements to characterize the reaction mechanisms of the core-RISC (RNA-induced silencing complex) composed of human Argonaute 2 and a small RNA. We found that target binding of core-RISC starts at the seed region, resulting in four distinct reaction pathways: target cleavage, transient binding, stable binding, and Argonaute unloading. The target cleavage requires extensive sequence complementarity and dramatically accelerates core-RISC recycling. The stable binding of core-RISC is efficiently established with the seed match only, providing a potential explanation for the seed-match rule of miRNA (microRNA) target selection. Target cleavage on perfect-match targets sensitively depends on RNA sequences, providing an insight into designing more efficient siRNAs (small interfering RNAs).

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Crossref · 10.1016/j.molcel.2015.04.027

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  • The degree of MRE complementarity determines whether there is AGO2-dependent slicing of target mRNA or miRISC-mediated translational inhibition and target mRNA decay.

    “The degree of MRE complementarity determines whether there is AGO2-dependent slicing of target mRNA or miRISC-mediated translational inhibition and target mRNA decay (47).”

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Authors
Jo, M. H., Shin, S., Jung, S.-R., Kim, E., Song, J.-J., & Hohng, S.
Affiliations
  • Seoul National University (KR)
  • Korea Advanced Institute of Science and Technology (KR)
Corresponding author
  • Song, Ji-Joon
  • Hohng, Sungchul
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2015-07
Volume
59
Issue
1
Pages
117-124
ISSN
1097-2765 (ISSN-L)
OpenAlex
W1480846517
Cited by
207
References
37
Citations by year
2026: 8 · 2025: 18 · 2024: 16 · 2023: 23 · 2022: 31 · 2021: 30 · 2020: 19 · 2019: 22 · 2018: 9 · 2017: 16 · 2016: 11 · 2015: 4
FWCI
5.79
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • 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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
Argonaute 2, RNA-induced silencing complex, RNA silencing, seed region, siRNA design, sequence complementarity, single-molecule fluorescence
MeSH terms
Base Sequence, Fluorescence, Humans, RNA, Small Interfering, RNA-Induced Silencing Complex, MicroRNAs, Argonaute Proteins

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