Cotranscriptional folding of RNA pseudoknots with different rates

Abstract

We investigate and compare the refolding and cotranscriptional folding process of RNA pseudoknot including PK5 pseudoknot, human telomerase RNA (hTR) pseudoknot and its mutants by using helix-based transition rate model and master equation. It is found that in the refolding process, the final states for PKWT and two mutants PK179AG/110CU and PK△U177 are all pseudoknots. However, the final state of mutant PKDC is a stable long helix. Furthermore, the cotranscriptional folding intermediates are quite different from refolding ones. The intermediate found in refolding process for PKWT is also shown during cotranscription. For PK179AG/110CU, the two intermediates in refolding are not found in cotranscriptional folding. For PK△U177, only one of the intermediates found in refolding is not observed in cotranscription. For PKDC, the unfolding sequence in the refolding process directly transits to native helix. Two intermediates are found during cotranscription. The populations of intermediates and native structure also depend on the cotranscriptional folding rate. All these findings can offer useful insights into cotranscription folding of hTR pseudoknot with different rates.