Crowner Anaiya, Smith Keely, DeSmet Marsha
Indiana University Simon Comprehensive Cancer Center American Cancer Society Post-Baccalaureate Diversity in Cancer Research Education Program, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Pathogens. 2024 Oct 2;13(10):863. doi: 10.3390/pathogens13100863.
R-loops are triple-stranded nucleic acid structures that occur when newly synthesized single-stranded RNA anneals to duplex DNA upon the collision of replication forks with transcription complexes. These RNA-DNA hybrids facilitate several transcriptional processes in the cell and have been described extensively in the literature. Recently, evidence has emerged that R-loops are key regulators of DNA tumor virus transcription and the replication of their lifecycle. Studies have demonstrated that R-loops on the Human Papillomavirus (HPV) genome must be resolved to maintain genome maintenance and avoid viral integration, a hallmark of HPV cancers. For Epstein-Barr virus (EBV), R-loops are formed at the to establish lytic replication. Structural maintenance of chromosome proteins 5/6 (SMC5/6) bind to these viral R-loops to repress EBV lytic replication. Most viruses in the order, such as KSHV, contain R-loop-forming sequences. In this perspective, we will describe the current, although limited, literature demonstrating the importance of RNA-DNA hybrids to regulate DNA virus transcription. We will also detail potential new areas of R-loop research and how these viruses can be used as tools to study the growing field of R-loops.
R环是三链核酸结构，当复制叉与转录复合物碰撞时，新合成的单链RNA与双链DNA退火结合就会形成R环。这些RNA-DNA杂交体促进细胞中的多种转录过程，并且在文献中已有广泛描述。最近，有证据表明R环是DNA肿瘤病毒转录及其生命周期复制的关键调节因子。研究表明，人乳头瘤病毒（HPV）基因组上的R环必须被解开，以维持基因组的稳定性并避免病毒整合，这是HPV相关癌症的一个标志。对于爱泼斯坦-巴尔病毒（EBV），R环在 处形成以建立裂解复制。染色体结构维持蛋白5/6（SMC5/6）与这些病毒R环结合以抑制EBV的裂解复制。疱疹病毒目中的大多数病毒，如卡波西肉瘤相关疱疹病毒（KSHV），都含有形成R环的序列。从这个角度来看，我们将描述目前虽有限但已有的文献，这些文献证明了RNA-DNA杂交体对调节DNA病毒转录的重要性。我们还将详细介绍R环研究的潜在新领域，以及这些病毒如何作为工具来研究R环这个不断发展的领域。
