Formation of frameshift-stimulating RNA pseudoknots is facilitated by remodeling of their folding intermediates.
Formation of frameshift-stimulating RNA pseudoknots is facilitated by remodeling of their folding intermediates.
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DOI：
10.1093/nar/gkab512
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发表时间：
2021-07-09
影响因子：
14.9
通讯作者：
Wen JD
中科院分区：
文献类型：
--
作者：
Hsu CF;Chang KC;Chen YL;Hsieh PS;Lee AI;Tu JY;Chen YT;Wen JD
程序性-1核糖体移码是病毒和细菌翻译的一种重要调控机制。它受编码区内的信使核糖核酸结构的刺激。由于该结构是由连续的翻译核糖体反复展开的，所以它能否每次都正确地折叠对其功能的发挥至关重要。通过单分子方法和分子动力学模拟，我们发现一个移码刺激RNA假结通过其上游茎S1和下游茎S2顺序折叠。在这条途径中，S2从下游折叠，并倾向于被困在中间体中。通过屏蔽最后几个核苷酸来模仿它们从翻译的核糖体中逐渐出现，S2可以被引导从上游区域折叠。结果表明，核糖体对mRNA的重折叠有明显的抑制作用，提示核糖体可能对其进行了调控。此外，掩蔽S1的前几个核苷酸有利于从S2折叠，并产生自然假结，这些假结足够稳定，足以恢复掩蔽的核苷酸。我们假设翻译核糖体可以将中间的mRNA结构重塑为稳定的构象，这反过来可能刺激核糖体的向后滑动。这支持了核糖体移帧的交互模型，并对先前的实验观察给出了有洞察力的解释。
Programmed –1 ribosomal frameshifting is an essential regulation mechanism of translation in viruses and bacteria. It is stimulated by mRNA structures inside the coding region. As the structure is unfolded repeatedly by consecutive translating ribosomes, whether it can refold properly each time is important in performing its function. By using single-molecule approaches and molecular dynamics simulations, we found that a frameshift-stimulating RNA pseudoknot folds sequentially through its upstream stem S1 and downstream stem S2. In this pathway, S2 folds from the downstream side and tends to be trapped in intermediates. By masking the last few nucleotides to mimic their gradual emergence from translating ribosomes, S2 can be directed to fold from the upstream region. The results show that the intermediates are greatly suppressed, suggesting that mRNA refolding may be modulated by ribosomes. Moreover, masking the first few nucleotides of S1 favors the folding from S2 and yields native pseudoknots, which are stable enough to retrieve the masked nucleotides. We hypothesize that translating ribosomes can remodel an intermediate mRNA structure into a stable conformation, which may in turn stimulate backward slippage of the ribosome. This supports an interactive model of ribosomal frameshifting and gives an insightful account addressing previous experimental observations.
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影响因子：
14.8
作者：
Lee, Hong-Won;Ryu, Ji Young;Yoon, Tae-Young
通讯作者：
Yoon, Tae-Young
DOI：
10.1073/pnas.0905046106
发表时间：
2009-08-04
影响因子：
11.1
作者：
Chen, Gang;Chang, Kung-Yao;Tinoco, Ignacio, Jr.
通讯作者：
Tinoco, Ignacio, Jr.
DOI：
10.1126/science.1225722
发表时间：
2012-10-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Frieda KL;Block SM
通讯作者：
Block SM
影响因子：
5.4
作者：
Kuhlmann, Micki M.;Chattopadhyay, Maitreyi;Simon, Anne E.
通讯作者：
Simon, Anne E.
影响因子：
3.5
作者：
Korniy, Natalia;Samatova, Ekaterina;Rodnina, Marina V.
通讯作者：
Rodnina, Marina V.