ABSTRACT

The capsid protein of dengue virus strain 2 (DENV2C) promotes nucleic acid structural rearrangements using chaperone activity. However, the role of DENV2C during the interaction of RNA elements in the conserved 5’ untranslated region (5’UTR) to the 3’ untranslated region (3’UTR) is still unclear. Thus, we investigated the effect of DENV2C on the annealing mechanism of two RNA hairpin elements from the 5’UTR to their complementary sequences during (+)/(-) ds-RNAformation and (+) RNA circularization. DENV2C was found to switch the annealing pathway for RNA elements involved in (+)/(-) ds-RNA formation, but not for RNA elements related to (+) RNA circularization. In addition, we also determined that DENV2C modulates intrinsic dynamics and reduces kinetically trapped unfavourable conformations of the 5’UTR sequence. Thus, our results provide mechanistic insights by which DENV2C chaperones the interactions between RNA elements at the 5’ and 3’ ends during genome recombination, a prerequisite for DENV replication.

摘要

登革热病毒株 2 (DENV2C) 的衣壳蛋白利用分子伴侣活性促进核酸结构重排。然而，DENV2C 在保守的 5' 非翻译区 (5'UTR) 与 3' 非翻译区 (3'UTR) 中的 RNA 元件相互作用过程中的作用仍不清楚。因此，我们研究了 DENV2C 在 (+)/(-) ds-RNA 形成和 (+) RNA 环化过程中对从 5'UTR 到它们的互补序列的两个 RNA 发夹元件的退火机制的影响。发现 DENV2C 改变了参与 (+)/(-) ds-RNA 形成的 RNA 元件的退火途径，但不能改变与 (+) RNA 环化相关的 RNA 元件。此外，我们还确定 DENV2C 调节内在动力学并减少动力学上捕获的 5'UTR 序列的不利构象。因此，