Programmed −1 ribosomal frameshifting (−1 PRF) is a translation mechanism that regulates the relative expression level of two proteins encoded on the same messenger RNA (mRNA). This regulation is commonly used by viruses such as coronaviruses and retroviruses but rarely by host human cells, and for this reason, it has long been considered as a therapeutic target for antiviral drug development. Understanding the molecular mechanism of −1 PRF is one step toward this goal. Minus-one PRF occurs with a certain efficiency when translating ribosomes encounter the specialized mRNA signal consisting of the frameshifting site and a downstream stimulatory structure, which impedes translocation of the ribosome. The impeded ribosome can still undergo profound conformational changes to proceed with translocation; however, some of these changes may be unique and essential to frameshifting. In addition, most stimulatory structures exhibit conformational dynamics and sufficient mechanical strength, which, when under the action of ribosomes, may in turn further promote −1 PRF efficiency. In this review, we discuss how the dynamic features of ribosomes and mRNA stimulatory structures may influence the occurrence of −1 PRF and propose a hypothetical frameshifting model that recapitulates the role of conformational dynamics.

中文翻译：

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从mRNA和核糖体构象动力学角度看程序化-1核糖体移码


程序性−1 核糖体移码 (−1 PRF) 是一种翻译机制，可调节同一信使 RNA (mRNA) 上编码的两种蛋白质的相对表达水平。这种调节通常被冠状病毒和逆转录病毒等病毒使用，但很少被宿主人类细胞使用，因此，它长期以来一直被认为是抗病毒药物开发的治疗靶点。了解−1 PRF 的分子机制是朝着这一目标迈出的一步。当翻译核糖体遇到由移码位点和下游刺激结构组成的专门 mRNA 信号时，负一 PRF 会以一定的效率发生，这会阻碍核糖体的易位。受阻的核糖体仍然可以发生深刻的构象变化以进行易位；然而，其中一些变化可能是独特的并且对于移码至关重要。此外，大多数刺激结构表现出构象动力学和足够的机械强度，当在核糖体的作用下，这可能反过来进一步提高-1 PRF效率。在这篇综述中，我们讨论了核糖体和 mRNA 刺激结构的动态特征如何影响 -1 PRF 的发生，并提出了一个假设的移码模型来概括构象动力学的作用。