Work

Regulation of transcription by R loop-nucleated transcription condensate assembly

Year: 2026

Type: article

Abstract: Prevalence of promoter paused R loops formed from frequent RNA PolII pausing in eukaryotic cells not only pose a significant threat to genomic stability, but also a potent regulator of transcription. In this review, we discuss how R loops act as both a product and regulator of transcription. Direct effects of R loops on transcription output are not well established, as studies on R loops are mainly focused on genomic instability triggered by accumulation of R loops. We dissect the evidence showing how R loops regulate transcription through a new manner: transcription condensates. Transcription condensates are dynamic, membraneless assemblies enriched with components of the transcription machinery, transcription factors, coactivators, and RNA-binding proteins (RBPs) that form at regulatory loci of critical, highly expressed genes to promote transcription rapidly and robustly. Coinciding at these condensate-forming regulatory loci are R loop hotspots, but this relationship and how they impact transcription as a unit remain to be defined. Recent developments suggest that R loops may act as multivalent seeds for transcription condensates through its modular structure, and as a binding platform for numerous RBPs containing phase separation-prone disordered regions. Interestingly, R loop processing may act as a double-edged sword to transcription: with partitioning of some factors into the transcription condensate promoting transcription, while others terminating transcription as a trade-off for protecting genomic integrity against pervasive R loops. Finally, we also summarize pathological conditions involving alterations of factors implicated in both R loop homeostasis and condensate dysregulation.

Source: Cell & Bioscience

DOI: 10.1186/s13578-026-01531-0

Authors: Raissa Regina Ng, Zhongyang Lin, Heng Wee Tan, Yan-Ming Xu, Andy T. Y. Lau

Institutions: Shantou University, Shantou University Medical College, Second Affiliated Hospital of Shantou University Medical College, First Affiliated Hospital of Shantou University Medical College

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $2,890

Funders: National Natural Science Foundation of China, Shantou University Medical College