Nascent RNA at the crossroad of transcription and replication

Ming-Yu Zhu; Yi-Zheng Zhang; Ting Guo; Jie Ren

doi:10.1016/j.tig.2025.05.010

Nascent RNA at the crossroad of transcription and replication

Trends Genet. 2025 Jun 25:S0168-9525(25)00130-1. doi: 10.1016/j.tig.2025.05.010. Online ahead of print.

Authors

Ming-Yu Zhu¹, Yi-Zheng Zhang¹, Ting Guo², Jie Ren³

Affiliations

¹ State Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, 200031, China; China National Center for Bioinformation, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² State Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, 200031, China; China National Center for Bioinformation, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China; School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China.
³ State Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, 200031, China; China National Center for Bioinformation, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: renjie@big.ac.cn.

PMID: 40571479
DOI: 10.1016/j.tig.2025.05.010

Abstract

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.

Keywords: R-loops; RNA modification; genome stability; nascent RNA; transcription stress; transcription–replication conflict.

Publication types

Review