丁型肝炎病毒(HDV)天然序列和G11C突变序列的转录折叠动力学研究

Cotranscriptional Folding Kinetics of the Wild-Type and G11C Mutation HDV Ribozyme

在转录折叠条件下,丁型肝炎病毒(HDV)的自剪切活性的发挥受到转录过程中形成的中间态结构、转录速率、突变位点等的影响.本文采用转录折叠动力学方法研究了HDV的天然(wild-type,wt)序列在不同转录速率下的转录折叠动力学行为,并分析了G11C突变对转录过程的影响.研究结果表明,虽然HDV的天然序列和G11C突变序列的转录折叠过程都存在快慢两条路径,但是对于HDV的天然序列,增大转录速率可以降低其慢速折叠路径上的RNA占据几率,而对于G11C突变序列,增大转录速率反而使得更多的RNA经过慢速路径形成天然态结构,并且在转录完全结束以后,HDV的天然序列要比G11C突变序列更快速地形成天然态结构.

Under the cotranscription conditions, there are many factors affect the self-cleavage activity of the hep- atitis delta virus （HDV）, such as the intermediate states, the transcription rate, the mutation sites and so on. In this study, we studied the folding kinetics of the wild-type （wt） HDV during the transcription with different transcription rates by the recently developed cotranscription folding kinetics theory. We also analysized the effects of the G11C mu- tation on the cotranscription folding process. The results suggest that, for the two sequences, there are two cotrans- cription folding pathways： a fast pathway and a slow pathway. For the wild-type sequence, less RNA sequence （RNAs） will fold through the slow pathway when increasing the transcription rate, while, for the G11C mutation se- quence, it is just the opposite. What＇ s more, at the end of the cotranscription, the wild-type HDV can form the native structures more quickly than G11C mutation sequence.