Publicaciones científicas

The chromatin-associated lncREST ensures effective replication stress response by promoting the assembly of fork signaling factors

01-feb-2024 | Revista: Nature Communications

Luisa Statello 1 2, José Miguel Fernandez-Justel 3 4, Jovanna González 3 4, Marta Montes 3 4, Alessia Ranieri 3 4, Enrique Goñi 3 4, Aina M Mas 3 4, Maite Huarte 5 6


Besides the well-characterized protein network involved in the replication stress response, several regulatory RNAs have been shown to play a role in this critical process. However, it has remained elusive whether they act locally at the stressed forks.

Here, by investigating the RNAs localizing on chromatin upon replication stress induced by hydroxyurea, we identified a set of lncRNAs upregulated in S-phase and controlled by stress transcription factors. Among them, we demonstrate that the previously uncharacterized lncRNA lncREST (long non-coding RNA REplication STress) is transcriptionally controlled by p53 and localizes at stressed replication forks. LncREST-depleted cells experience sustained replication fork progression and accumulate un-signaled DNA damage.

Under replication stress, lncREST interacts with the protein NCL and assists in engaging its interaction with RPA. The loss of lncREST is associated with a reduced NCL-RPA interaction and decreased RPA on chromatin, leading to defective replication stress signaling and accumulation of mitotic defects, resulting in apoptosis and a reduction in tumorigenic potential of cancer cells. These findings uncover the function of a lncRNA in favoring the recruitment of replication proteins to sites of DNA replication.

CITA DEL ARTíCULO Nat Commun. 2024 Feb 1;15(1):978. doi: 10.1038/s41467-024-45183-5.

Nuestros autores

Dra. Luisa Statello
Dr. José Miguel Fernández Justel
Técnico de Investigación Bioinformático Grupo de Investigación en ARN No Codificante y Genoma del Cáncer
Dra. Jovanna González Rojas
Marta Montes Resano
Investigador predoctoral del Programa de Terapia Génica del Cima Universidad de Navarra
Enrique Goñi Echeverría