Many Activities, One Structure: Functional Plasticity of Ribozyme Folds.
Many Activities, One Structure: Functional Plasticity of Ribozyme Folds.
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DOI：
10.3390/molecules21111570
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发表时间：
2016-11-18
期刊：
影响因子：
--
通讯作者：
Ferré-D'Amaré AR
中科院分区：
文献类型：
--
作者：
Lau MW;Ferré-D'Amaré AR
催化RNA或核酶参与了许多基本的生物过程，如RNA基因组和可移动遗传元件的复制、RNA剪接、翻译和RNA降解。核酶的功能需要在定义的三维（3D）结构中形成带有RNA功能基团装饰的活性位点。rna的基因型（序列）最终决定了它们采用的3D结构（作为其环境条件的函数）。这些3D结构，反过来，产生生物化学活性，这可以通过催化重排或与其他分子结合进一步细化它们。非周期性线性聚合物（如RNA）的适应度景观将其主要结构与表型联系起来。核酶分析的两个主要挑战是将所有可能的基因型映射到它们相应的催化活性（即通过实验确定它们的适合度景观），以及了解它们的基因型和三维结构是否能够支持多种不同的催化功能。最近，采用体外进化方法、高通量测序和晶体结构测定的综合实验结果暗示了这两个问题的答案：虽然核糖酶的适应度景观是崎岖的，这意味着它们的催化活性不能通过序列空间的平滑轨迹来优化，但一旦RNA达到稳定的三维折叠，通过基因型的微小变化，它就可以被赋予明显不同的生化活性。高度结构化rna的这种功能可塑性可能对生物体适应选择压力的剧烈变化或开发新的生物技术工具特别有利。
Catalytic RNAs, or ribozymes, are involved in a number of essential biological processes, such as replication of RNA genomes and mobile genetic elements, RNA splicing, translation, and RNA degradation. The function of ribozymes requires the formation of active sites decorated with RNA functional groups within defined three-dimensional (3D) structures. The genotype (sequence) of RNAs ultimately determines what 3D structures they adopt (as a function of their environmental conditions). These 3D structures, in turn, give rise to biochemical activity, which can further elaborate them by catalytic rearrangements or association with other molecules. The fitness landscape of a non-periodic linear polymer, such as RNA, relates its primary structure to a phenotype. Two major challenges in the analysis of ribozymes is to map all possible genotypes to their corresponding catalytic activity (that is, to determine their fitness landscape experimentally), and to understand whether their genotypes and three-dimensional structures can support multiple different catalytic functions. Recently, the combined results of experiments that employ in vitro evolution methods, high-throughput sequencing and crystallographic structure determination have hinted at answers to these two questions: while the fitness landscape of ribozymes is rugged, meaning that their catalytic activity cannot be optimized by a smooth trajectory in sequence space, once an RNA achieves a stable three-dimensional fold, it can be endowed with distinctly different biochemical activities through small changes in genotype. This functional plasticity of highly structured RNAs may be particularly advantageous for the adaptation of organisms to drastic changes in selective pressure, or for the development of new biotechnological tools.
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DOI：
10.1038/nrg2749
发表时间：
2010-03
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
8.6
作者：
Ferré-D'Amaré AR
通讯作者：
Ferré-D'Amaré AR
影响因子：
3.5
作者：
JOYCE, GF
通讯作者：
JOYCE, GF
影响因子：
15
作者：
Lau, MWL;Cadieux, KEC;Unrau, PJ
通讯作者：
Unrau, PJ
影响因子：
2.9
作者：
Davis JH;Dunican BF;Strobel SA
通讯作者：
Strobel SA