Noncoding RNA in the Coordination of DNA Replication and Genomic Stability

Nuclear RNAs, whether coding or noncoding, interact closely with chromatin, influencing chromatin-related processes, with strong implications for cancer emergence and progression. However, their role in DNA replication and genomic stability is still not fully understood. Our recent research uncovered that RNAs are involved in initiating DNA replication. Specifically, the ORC1 subunit of the human Origin Recognition Complex binds with RNAs transcribed from genes containing origins at their transcription start sites. These RNAs regulate ORC1's phosphorylation and chromatin dissociation, essential for efficient replication origin activation. Beyond initiation, new findings highlight long non-coding RNAs as involved in DNA replication and its stress response. Intriguingly, we found a new class of repetitive long noncoding RNAs enriched at replication forks. These lncRNAs negatively impact DNA synthesis by slowing its rate and reducing efficiency, while favoring the correct packaging of chromatin. I will present our latest findings on these noncoding RNAs' distinct roles, revealing their dynamic functions in coordinating transcription and replication processes in human cells.