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Peer-reviewedCC BY 4.0Molecular Cell

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

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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BibTeX
@article{lopezperrote2026concr,
  title = {{CONCR lncRNA organizes a 3′-end structural domain that engages DDX11 for DNA replication and sister chromatid cohesion}},
  author = {Andrés López-Perrote and Eva María Martín-Cuevas and José Antonio Mérida-Cerro and Clara Aicart-Ramos and Ana González-Corpas and Jovanna González and Johanne Le Coq and Jasminka Boskovic and Isabel Chillón and Oscar Llorca and Fernando Moreno-Herrero and Maite Huarte},
  journal = {Molecular Cell},
  year = {2026},
  month = aug,
  doi = {10.1016/j.molcel.2026.08.004},
  url = {https://hal.science/hal-05829477v1},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - CONCR lncRNA organizes a 3′-end structural domain that engages DDX11 for DNA replication and sister chromatid cohesion
AU  - Andrés López-Perrote
AU  - Eva María Martín-Cuevas
AU  - José Antonio Mérida-Cerro
AU  - Clara Aicart-Ramos
AU  - Ana González-Corpas
AU  - Jovanna González
AU  - Johanne Le Coq
AU  - Jasminka Boskovic
AU  - Isabel Chillón
AU  - Oscar Llorca
AU  - Fernando Moreno-Herrero
AU  - Maite Huarte
PY  - 2026
DA  - 2026/08/28
JO  - Molecular Cell
DO  - 10.1016/j.molcel.2026.08.004
UR  - https://hal.science/hal-05829477v1
AB  - 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.
SN  - 1097-2765
SN  - 1097-4164
ER  -