Nascent RNA at the crossroad of transcription and replication

The concurrent processes of DNA replication and RNA transcription pose a significant challenge to genome integrity. Nascent RNA, the newly synthesized transcript, is emerging as a critical determinant of transcription–replication conflict (TRC) outcomes, exerting influence through its modifications, its ability to form RNA:DNA hybrids (R-loops), its regulation of chromatin structure, and its interaction with protein complexes at the transcription–replication interface. Here, we synthesize recent advances on how nascent RNA modulates transcription dynamics, replication fork progression, and genome stability. We explore its paradoxical roles – both inducing replication stress and orchestrating protective responses – highlighting how RNA processing factors mitigate TRCs. Finally, we emphasize the need for innovative technologies to dissect the dynamic and context-dependent roles of nascent RNA and therapeutic potential for genomic instability-linked diseases.