2022,
Proceedings of the National Academy of Sciences.
DOI:
10.1073/pnas.2112677119
Thoughts on how to think (and talk) about RNA structure
Quentin Vicens, Jeffrey S. Kieft
Abstract:
Recent events have pushed RNA research into the spotlight. Continued discoveries of RNA with unexpected diverse functions in healthy and diseased cells, such as the role of RNA as both the source and countermeasure to a severe acute respiratory syndrome coronavirus 2 infection, are igniting a new passion for understanding this functionally and structurally versatile molecule. Although RNA structure is key to function, many foundational characteristics of RNA structure are misunderstood, and the default state of RNA is often thought of and depicted as a single floppy strand. The purpose of this perspective is to help adjust mental models, equipping the community to better use the fundamental aspects of RNA structural information in new mechanistic models, enhance experimental design to test these models, and refine data interpretation. We discuss six core observations focused on the inherent nature of RNA structure and how to incorporate these characteristics to better understand RNA structure. We also offer some ideas for future efforts to make validated RNA structural information available and readily used by all researchers.
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2023-09-30 22:52:00
尹志:
#paper https://doi.org/10.1073/pnas.2112677119 Thoughts on how to think (and talk) about RNA structure。mRNA疫苗的出现，再一次唤起了生物学家们对RNA结构与功能研究的热情。本文强调了重新审视rna，开展未来更多研究的重要性，反思了当前对rna结构与功能理解上可能存在的误区，并结合自己的经验，提出了6条rna研究上值得注意的点，这些观点对未来rna研究提供了一个很有价值的方向。rna的复杂性及目前的开放性是一个特别吸引计算研究者入坑的原因。传统上将rna看做一条松垮的面条的方式目前看来恐怕不能很好的描述rna的结构，rna折叠的预测目前存在非常大的挑战或者说研究空间，据我所知，目前rna折叠连二级结构都做不好，那三级结构呢？即使结构测定相对容易的情况下，作为计算工作者，能不能很好的跟进？作者在文中多次强调了rna的“unstructed”的表述问题，所谓的非结构给rna的结构预测反而提出了更大挑战：所谓“Inherently Structured”Does Not Mean “Static”， 从计算角度而言，rna的骨架约束变少，自由能landscape梯度较低，那么给计算优化带来了很多有趣的问题，面对大量的局部最优，有不有更合适的优化算法？特别是rna的动态敏感性，怎么在实际预测中考虑
这些因素，如何建模这些环境影响？Non-Watson–Crick Pairing在在RNA的功能和调控中的作用如何被考虑，等等问题。正如作者在文末呼吁的：RNA has gone mainstream, solet’s make sure RNA structure properties return to thefront seat。