Coordinated initiation of DNA replication is essential to ensure efficient and timely DNA synthesis. Yet, molecular mechanism describing how replication initiation is coordinated in eukar-yotic cells is not completely understood. Herein, we present data demonstrating a novel feature of RNAs transcribed in the proximity of actively replicating gene loci. We show that RNAs aN-Choring ORC1 (ANCORs) to the histone variant H2A.Z are licensors of the DNA replication process. This ANCOR-H2A.Z interaction is essential for cells to initiate duplication of their ge-netic material. Widespread and locus-specific perturbations of these transcripts correlate with anomalous replication patterns and a notable loss of the H2A.Z replicative marker at the origin site. Collectively, we present a previously undescribed RNA-mediated mechanism that is associ-ated with the generation of active replication origins in eukaryotic cells. Our findings delineate a strategy to modulate the origins of replication in human cells at a local and global level, with potentially broad biomedical implications.