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CONCR lncRNA organizes a 3'-end structural domain that engages DDX11 for DNA replication and sister chromatid cohesion.

Andrés López-Perrote·Eva María Martín-Cuevas·José Antonio Mérida-Cerro·Clara Aicart-Ramos·Ana González-Corpas·Jovanna González·Johanne Le Coq·Jasminka Boskovic·Isabel Chillón·Oscar Llorca·Fernando Moreno-Herrero·Maite Huarte
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Abstract

CONCR (DDX11-AS1) is a long noncoding RNA (lncRNA) necessary for the establishment of sister chromatid cohesion. Despite its activity, whether it contains structural elements essential for its function remains unknown. We determined CONCR structural organization and its functional relevance by integrating selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP), atomic force microscopy (AFM), evolutionary analyses, cryo-electron microscopy (cryo-EM), and cellular genetic studies. We found that CONCR molecular topology is modular, with highly structured domains connected by flexible linkers. A large 3'-end domain is responsible for binding to DDX11 helicase, can trigger DDX11 ATPase activity, and is essential for proper DNA replication and sister chromatid cohesion. This 3' end comprises two helical arms connecting two multiway junctions with structural motifs conserved among all primate groups and required for DDX11 binding and sister chromatid cohesion. Our results highlight the critical role of RNA structure in CONCR function, with a highly structured 3'-end domain acting as a loading and activation platform for DDX11 helicase.

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DEAD-box RNA HelicasesDNA ReplicationHumansChromatidsRNA, Long NoncodingProtein BindingNucleic Acid ConformationMicroscopy, Atomic ForceCryoelectron MicroscopyStructure-Activity RelationshipHeLa CellsSister Chromatid ExchangeModels, MolecularDNA HelicasesAFMCONCRDDX11DNA replicationRNA structureSHAPE-MaPcryo-EMgenomic stabilitylncRNAsister chromatid cohesionJournal Article

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Andrés López-Perrote, Eva María Martín-Cuevas, José Antonio Mérida-Cerro, Clara Aicart-Ramos, Ana González-Corpas, Jovanna González, Johanne Le Coq, Jasminka Boskovic, Isabel Chillón, Oscar Llorca, Fernando Moreno-Herrero, Maite Huarte. 2026-08-28. CONCR lncRNA organizes a 3'-end structural domain that engages DDX11 for DNA replication and sister chromatid cohesion.. https://doi.org/10.1016/j.molcel.2026.08.004

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