ArticleCell reports2024
Target cleavage and gene silencing by Argonautes with cityRNAs.
Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- 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 · 2026Article
- Structural basis for RISC assembly of human Argonaute2.Molecular cell · 2026Article
- Article
- The E3 ubiquitin ligase mechanism specifying target-directed microRNA degradation.bioRxiv : the preprint server for biology · 2026Article
- Triplexes Color the Chromaverse by Modulating Nucleosome Phasing and Anchoring Chromatin Condensates.International journal of molecular sciences · 2025Review
- RNA Structure: Past, Future, and Gene Therapy Applications.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
TinyRNAs (tyRNAs) are ≤17-nt guide RNAs associated with Argonaute proteins (AGOs), and certain 14-nt cleavage-inducing tyRNAs (cityRNAs) catalytically activate human Argonaute3 (AGO3). We present the crystal structure of AGO3 in complex with a cityRNA, 14-nt miR-20a, and its complementary target, revealing a different trajectory for the guide-target duplex from that of its ∼22-nt microRNA-associated AGO counterpart. cityRNA-loaded Argonaute2 (AGO2) and AGO3 enhance their endonuclease activity when the immediate 5' upstream region of the tyRNA target site (UTy) includes sequences with low affinity for AGO. We propose a model where cityRNA-loaded AGO2 and AGO3 efficiently cleave fully complementary tyRNA target sites unless they directly recognize the UTy. To investigate their gene silencing, we devised systems for loading endogenous AGOs with specific tyRNAs and demonstrated that, unlike microRNAs, cityRNA-mediated silencing heavily relies on target cleavage. Our study uncovered that AGO exploits cityRNAs for target recognition differently from microRNAs and alters gene silencing.
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Registered trials
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.