Evidence map›Paper›PMID 42190652›Full record

ArticleMolecular cell2026

Structural basis for RISC assembly of human Argonaute2.

Huaqun Zhang, Vishal Annasaheb Adhav, Audrey C Kehling, Andrew Savidge, Zhangfei Shen, Tian-Min Fu, Kotaro Nakanishi

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Central guide-target pairing activates human Argonaute2 by uncoupling the N-PAZ and MID-PIWI lobes.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Huaqun ZhangDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
Vishal Annasaheb AdhavDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
Audrey C KehlingDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
Andrew SavidgeOhio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
Zhangfei ShenDepartment of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA.
Tian-Min FuOhio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA; Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA; Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA; Department of Pathology, UMass Chan Medical School, Worcester, MA 01655, USA.
Kotaro NakanishiDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA; Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA; Molecular, Cellular and Developmental Biology, The Ohio State University, Columbus, OH 43210, USA. Electronic address: nakanishi.9@osu.edu.

Funding

Target specificity of human RNA-induced silencing complexR01GM124320 · NIGMS · OHIO STATE UNIVERSITY · PI NAKANISHI, KOTARO · 2017 to 2025
$3.1M
Cellular, molecular, and biochemical sciences training grantT32GM141955 · NIGMS · OHIO STATE UNIVERSITY · PI Jane Elizabeth Jackman, JESSE J KWIEK · 2021 to 2026
$2.2M
Structural and molecular basis for cityRNA(cleavage-inducing tiny RNA)-directed RNA cleavage by AGO3R01GM138997 · NIGMS · OHIO STATE UNIVERSITY · PI NAKANISHI, KOTARO · 2020 to 2025
$2.1M
Structure and Mechanism of Gene Regulation by Small Noncoding RNAsR35GM161485 · NIGMS · OHIO STATE UNIVERSITY · PI Kotaro Nakanishi · 2026 to 2026
$420k
NIGMS NIH HHS R01 GM124320NIGMS NIH HHS R01 GM138997NIGMS NIH HHS R35 GM161485NIGMS NIH HHS T32 GM141955
6 · The paper itself

Abstract

Argonaute proteins (AGOs) load small RNA duplexes and select one strand to form the RNA-induced silencing complex (RISC), but the mechanism of assembly remains unclear. We report four cryogenic-electron microscopy structures of human AGO2 bound to a small interfering RNA (siRNA) duplex, which captures previously unanticipated intermediates. Unexpectedly, only the MID-PIWI lobe secures one duplex end, while α-helix 14 probes its stability. When the N domain reaches the opposite end, the L1 hairpin and Stalk wedge into the duplex and the PAZ domain engages the guide 3' end. This configuration peels the passenger from its 5' end while leaving it paired to the guide seed. AGO2 completely ejects the passenger by replacing it even with partially complementary target RNAs. This target-assisted passenger ejection (TAPE) also operates for the cleaved passenger strand. Our study uncovers that mRNAs are bifunctional molecules that not only serve as targets of RISCs but also help drive RISC assembly.

Indexed as

Argonaute ProteinsRNA-Induced Silencing ComplexRNA, Small InterferingCryoelectron MicroscopyHumansModels, MolecularProtein BindingRNA, MessengerAGO2 protein, humanArgonaute ProteinsRNA-Induced Silencing ComplexRNA, MessengerRNA, Small InterferingArgonautebiotechnologygene silencingmiRNARISCRISC assemblyRNAiRNA-induced silencing complexsiRNAtherapeutics

Identifiers

PMID42190652
PMCPMC13306894

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.