Vicens Quentin, Kieft Jeffrey S, Rissland Olivia S
Department of Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Department of Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Mol Cell. 2018 Dec 6;72(5):805-812. doi: 10.1016/j.molcel.2018.10.047.
Communication between the 5' and 3' ends of mature eukaryotic mRNAs lies at the heart of gene regulation, likely arising at the same time as the eukaryotic lineage itself. Our view of how and why it occurs has been shaped by elegant experiments that led to nearly universal acceptance of the "closed-loop model." However, new observations suggest that this classic model needs to be reexamined, revised, and expanded. Here, we address fundamental questions about the closed-loop model and discuss how a growing understanding of mRNA structure, dynamics, and intermolecular interactions presents new experimental opportunities. We anticipate that the application of emerging methods will lead to expanded models that include the role of intrinsic mRNA structure and quantitative dynamic descriptions of 5'-3' proximity linked to the functional status of an mRNA and will better reflect the messy realities of the crowded and rapidly changing cellular environment.
成熟真核生物mRNA的5'端和3'端之间的通讯是基因调控的核心,可能与真核生物谱系本身同时出现。我们对于它如何以及为何发生的看法,是由一些精妙的实验塑造而成的,这些实验使得“闭环模型”几乎被普遍接受。然而,新的观察结果表明,这个经典模型需要重新审视、修订和扩展。在这里,我们探讨有关闭环模型的基本问题,并讨论对mRNA结构、动力学和分子间相互作用日益深入的理解如何带来新的实验机会。我们预计,新兴方法的应用将产生扩展模型,这些模型将包括内在mRNA结构的作用以及与mRNA功能状态相关的5'-3'接近度的定量动态描述,并且将更好地反映拥挤且快速变化的细胞环境中的复杂现实。