Tao Peng, Si Yunda, Xia Jie, Xiao Yi
Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, Hangzhou; University of Chinese Academy of Sciences, Beijing, China.
School of Physics, Huazhong University of Science and Technology, Wuhan, China.
PLoS Comput Biol. 2025 Sep 8;21(9):e1013472. doi: 10.1371/journal.pcbi.1013472. eCollection 2025 Sep.
The divergence in folding pathways between RNA co-transcriptional folding (CTF) and free folding (FF) is crucial for understanding dynamic functional regulation of RNAs. Here, we developed a simplified all-atom molecular dynamics framework to systematically compare the folding kinetics of an RNA hairpin (PDB:1ZIH) under CTF and FF conditions. By analyzing over 800 microseconds of simulated trajectory, we found that despite convergence to identical native conformations across CTF simulations (with varied transcription rates) and FF simulations, they exhibit distinct preferences for the folding pathways defined by the order of base-pair formation. Conformational space analysis shows that CTF biases the folding pathway by adopting more compact conformations than FF. Our findings provide atomic-scale insights into how temporal-spatial coupling of transcription and folding diversifies RNA folding dynamics.
RNA共转录折叠（CTF）和自由折叠（FF）之间折叠途径的差异对于理解RNA的动态功能调控至关重要。在此，我们开发了一个简化的全原子分子动力学框架，以系统地比较RNA发夹（PDB:1ZIH）在CTF和FF条件下的折叠动力学。通过分析超过800微秒的模拟轨迹，我们发现尽管在CTF模拟（转录速率不同）和FF模拟中都收敛到相同的天然构象，但它们对由碱基对形成顺序定义的折叠途径表现出不同的偏好。构象空间分析表明，CTF通过采用比FF更紧凑的构象来偏向折叠途径。我们的研究结果为转录和折叠的时空耦合如何使RNA折叠动力学多样化提供了原子尺度的见解。
