biostudies-literatureMartinez-Balsalobre EMinistry of Science and Innovation. SpainMinistry of Economy and Competitiveness | Instituto de Salud Carlos IIIFundación Ramón Areces Consejeria de Sanidad de la Región de Murcia. ZEBER5912https://www.ebi.ac.uk/biostudies/studies/S-EPMC10516865biostudies-literatureUnknown14(1)Telomerase RNA (TERC) has a noncanonical function in myelopoiesis binding to a consensus DNA binding sequence and attracting RNA polymerase II (RNA Pol II), thus facilitating myeloid gene expression. The CR4/CR5 domain of TERC is known to play this role, since a mutation of this domain found in dyskeratosis congenita (DC) patients decreases its affinity for RNA Pol II, impairing its myelopoietic activity as a result. In this study, we report that two aptamers, short single-stranded oligonucleotides, based on the CR4/CR5 domain were able to increase myelopoiesis without affecting erythropoiesis in zebrafish. Mechanistically, the aptamers functioned as full terc; that is, they increased the expression of master myeloid genes, independently of endogenous terc, by interacting with RNA Pol II aNature communicationsTelomerase RNA-based aptamers restore defective myelopoiesis in congenital neutropenic syndromes.PMC10516865PI19/00188PI22/00861Garcia-Moreno DGarcia-Castillo JMulero VNaranjo-Sanchez ECayuela MLFernandez-Lajarin MAlcaraz-Perez FMartinez-Balsalobre EBlasco MAfalseTelomerase RNA-based aptamers restore defective myelopoiesis in congenital neutropenic syndromes.Telomerase RNA (TERC) has a noncanonical function in myelopoiesis binding to a consensus DNA binding sequence and attracting RNA polymerase II (RNA Pol II), thus facilitating myeloid gene expression. The CR4/CR5 domain of TERC is known to play this role, since a mutation of this domain found in dyskeratosis congenita (DC) patients decreases its affinity for RNA Pol II, impairing its myelopoietic activity as a result. In this study, we report that two aptamers, short single-stranded oligonucleotides, based on the CR4/CR5 domain were able to increase myelopoiesis without affecting erythropoiesis in zebrafish. Mechanistically, the aptamers functioned as full terc; that is, they increased the expression of master myeloid genes, independently of endogenous terc, by interacting with RNA Pol II a2023-01-01T00:00:00Z2023 Sep2026-06-04T06:33:00.344Z2024-11-15T17:13:05.88ZS-EPMC105168653773723710.1038/s41467-023-41472-7