Regulation of programmed ribosomal frameshifting by co-translational refolding RNA hairpins.
Regulation of programmed ribosomal frameshifting by co-translational refolding RNA hairpins.
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DOI：
10.1371/journal.pone.0062283
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chang KY
中科院分区：
文献类型：
--
作者：
Cho CP;Lin SC;Chou MY;Hsu HT;Chang KY
RNA结构被解开以进行解码。在这个过程中，他们可以暂停伸长的核糖体进行调节。一个例子是-1程序性核糖体移码的刺激，导致在伸长过程中读框的3‘方向滑动，由移码位置下游的特定假结刺激物。通过对最近发现的SARS冠状病毒−1移码位点上游调控元件的研究表明，具有发夹形成潜力的最小功能元件足以下调−1移码活性。突变以破坏或恢复潜在发夹茎中的碱基对，表明在体外和293T细胞中，−1移码衰减需要碱基对的形成。发夹的衰减效率取决于它的稳定性和与移框位置的接近程度，但它对E位序列的变化不敏感。此外，使用双荧光素酶分析，可以表明，发夹刺激+1移位时，在酵母中的+1移位位置的上游。研究表明，发夹确实是一种顺式作用的程控读框开关调制器。这一结果为深入了解−1移码刺激和衰减的机制提供了依据。由于上游发夹在下游刺激物之前解开(由行进的核糖体)，这项研究发现表明了一种新的翻译调节模式，这种模式是由核糖体解卷的RNA发夹在伸长过程中的改建茎介导的。
RNA structures are unwound for decoding. In the process, they can pause the elongating ribosome for regulation. An example is the stimulation of -1 programmed ribosomal frameshifting, leading to 3′ direction slippage of the reading-frame during elongation, by specific pseudoknot stimulators downstream of the frameshifting site. By investigating a recently identified regulatory element upstream of the SARS coronavirus (SARS-CoV) −1 frameshifting site, it is shown that a minimal functional element with hairpin forming potential is sufficient to down-regulate−1 frameshifting activity. Mutagenesis to disrupt or restore base pairs in the potential hairpin stem reveals that base-pair formation is required for−1 frameshifting attenuation in vitro and in 293T cells. The attenuation efficiency of a hairpin is determined by its stability and proximity to the frameshifting site; however, it is insensitive to E site sequence variation. Additionally, using a dual luciferase assay, it can be shown that a hairpin stimulated +1 frameshifting when placed upstream of a +1 shifty site in yeast. The investigations indicate that the hairpin is indeed a cis-acting programmed reading-frame switch modulator. This result provides insight into mechanisms governing−1 frameshifting stimulation and attenuation. Since the upstream hairpin is unwound (by a marching ribosome) before the downstream stimulator, this study’s findings suggest a new mode of translational regulation that is mediated by the reformed stem of a ribosomal unwound RNA hairpin during elongation.
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