Telomerase RNA recruits RNA polymerase II to target gene promoters to enhance myelopoiesis
Year: 2021
Type: article
Abstract: Significance Dyskeratosis congenita (DC) is a rare inherited bone marrow failure and cancer predisposition syndrome caused by mutations in telomerase or telomeric proteins. Although all patients show telomere shortening, the symptoms are highly variable and, therefore, other mechanisms have to be involved. Here, we report that telomerase RNA component ( TERC ) regulates the expression of master myeloid genes in zebrafish and humans by recruiting the transcription machinery. Induced pluripotent stem cells derived from DC patients with a TERC mutation in a specific domain, the CR4-CR5, shows impaired myelopoiesis, while those from DC patients with mutation in telomerase catalytic subunit differentiated normally. Our findings reveal a target for personalized and precision medicine approaches for DC patients.
Authors: Jesús García-Castillo, Francisca Alcaraz-Pérez, Elena Martínez-Balsalobre, Diana García-Moreno, Marlies P. Rossmann, Miriam Fernández-Lajarín, Manuel Bernabé-García, Ana B. Pérez-Oliva, Virginia C. Rodríguez-Cortez, Clara Bueno, Isaac Adatto, Suneet Agarwal, Pablo Menéndez, Leonard I. Zon, Victoriano Mulero, María L. Cayuela
Institutions: Instituto Murciano de Investigación Biosanitaria, Hospital Universitario Virgen de la Arrixaca, Instituto de Salud Carlos III, Centre for Biomedical Network Research on Rare Diseases, Universidad de Murcia, Boston Children's Hospital, Harvard University, Dana-Farber Cancer Institute, Institució Catalana de Recerca i Estudis Avançats, Josep Carreras Leukaemia Research Institute, Centro de Investigación Biomédica en Red de Cáncer, Universitat de Barcelona, Howard Hughes Medical Institute
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1499303479, G3745117842, Mecanismos implicados en las alteraciones hematopoyéticas y cáncer en la Disqueratosos congénita. Búsqueda de terapias, G4798297891, G503615948, Transcriptional response to signaling during hematopoiesis, Nuevas y viejas funciones del Componente de RNA de la Telomerasa en Hematopoyesis y Envejecimiento, Estrategias terapéuticas, G7214662604, Stem cells for therapeutics discovery in genetic blood disorders
OpenAlex ID: W3187583892