Effect of pausing on the cotranscriptional folding kinetics of RNAs

The pausing event in RNA molecule folding that occurs during the cotranscription process plays a critical role in cellular RNA function. Based on Conformational Resampling through Kinetic Relaxation (CRKR), this paper investigates a method to reveal the specifics of pausing for RNA cotranscriptional folding of 117-nucleotide E. coli SRP RNA and 73-nucleotide HIV-1 TAR RNA. It can be inferred from the results that pausing events generate valid cotranscriptional conformational rearrangement to protect the function structures and influence the folding pathway, which is remarkably consistent with the experimental results. Additionally, different transcription speeds result in different levels of protection capability. The folding pathway or conformational rearrangement can also be affected by a change in transcription speed after pausing site. These findings illuminate that RNAs with functional structures undergo complex rearrangement folding in pausing events, and different RNAs prefer different speeds for specific folding pathways. Moreover, pausing in particular circumstances can be employed to regulate the population of final functional structures. In conclusion, this paper offers fresh perspectives on the pausing event in the cotranscriptional folding of RNAs.