美国哥伦比亚大学Hashim M. Al-Hashimi等研究人员合作发现，RNA构象倾向性决定细胞的活动。相关论文于2023年5月17日在线发表在《自然》杂志上。
研究人员系统地改变并确定了HIV-1 TAR RNA形成与蛋白质结合的构象的倾向性。这些倾向性定量地预测了TAR与Tat蛋白的RNA结合区的结合亲和力，并预测了HIV-1 Tat在细胞中依赖的转导程度。这些结果确立了基于集合的构象倾向性在细胞活动中的作用，并揭示了一个由特别罕见和短命的RNA构象状态驱动的细胞过程的例子。
据悉，细胞过程是生物大分子之间相互作用的产物，它们联合起来形成具有生物活性的复合体。这些相互作用是由分子间的接触介导的，如果这些接触被破坏，就会导致细胞生理学的改变。然而，分子间接触的形成几乎普遍需要改变相互作用的生物分子的构象。因此，结合亲和力和细胞活性主要取决于接触的强度和形成具有结合能力的构象状态的固有倾向。因此，构象不利在生物学中无处不在，并且必须知道构象不利以便对蛋白质和核酸相互作用的结合能量进行定量建模。然而，概念和技术上的限制阻碍了人们剖析和定量测量构象倾向性如何影响细胞活动的能力。
附：英文原文
Title: RNA conformational propensities determine cellular activity
Author: Ken, Megan L., Roy, Rohit, Geng, Ainan, Ganser, Laura R., Manghrani, Akanksha, Cullen, Bryan R., Schulze-Gahmen, Ursula, Herschlag, Daniel, Al-Hashimi, Hashim M.
Issue&Volume: 2023-05-17
Abstract: Cellular processes are the product of interactions between biomolecules, which associate to form biologically active complexes1. These interactions are mediated by intermolecular contacts, which if disrupted, lead to alterations in cell physiology. Nevertheless, the formation of intermolecular contacts nearly universally requires changes in the conformations of the interacting biomolecules. As a result, binding affinity and cellular activity crucially depend both on the strength of the contacts and on the inherent propensities to form binding-competent conformational states2,3. Thus, conformational penalties are ubiquitous in biology and must be known in order to quantitatively model binding energetics for protein and nucleic acid interactions4,5. However, conceptual and technological limitations have hindered our ability to dissect and quantitatively measure how conformational propensities affect cellular activity. Here we systematically altered and determined the propensities for forming the protein-bound conformation of HIV-1 TAR RNA. These propensities quantitatively predicted the binding affinities of TAR to the RNA-binding region of the Tat protein and predicted the extent of HIV-1 Tat-dependent transactivation in cells. Our results establish the role of ensemble-based conformational propensities in cellular activity and reveal an example of a cellular process driven by an exceptionally rare and short-lived RNA conformational state.
DOI: 10.1038/s41586-023-06080-x
Source: https://www.nature.com/articles/s41586-023-06080-x
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
