Cotranscriptional folding of RNA pseudoknots with different rates.

For human telomerase RNA(hTR) pseudoknot PK WT and its mutants PK △U177 , PK 179AG/110CU, PK DC , the cotranscriptional folding kinetics are quite different from refolding, which causes different levels of telomerase activity. For PK DC , the absence of pseudoknot causes the reduction in telomerase activity. And it is also found that the population of intermediates during cotranscriptional folding largely depend on the cotranscription rate. [Display omitted] • For human telomerase RNA(hTR) pseudoknot PK WT , three intermediates have been found in cotranscriptional folding. • For PK △U177 , the population of the pseudoknot are smaller, which causes the telomerase activity more weaker. For PK DC , the native structure is a stable long helix. • The population of intermediates during cotranscriptional folding largely depend on the cotranscription rate. 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 PK WT and two mutants PK 179AG/110CU and PK △U177 are all pseudoknots. However, the final state of mutant PK DC is a stable long helix. Furthermore, the cotranscriptional folding intermediates are quite different from refolding ones. The intermediate found in refolding process for PK WT is also shown during cotranscription. For PK 179AG/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 PK DC , 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. [ABSTRACT FROM AUTHOR]