Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, 50 South Drive, Bethesda, MD 20892, USA.
Molecules. 2020 Jun 23;25(12):2881. doi: 10.3390/molecules25122881.
In comparison with the pervasive use of protein dimers and multimers in all domains of life, functional RNA oligomers have so far rarely been observed in nature. Their diminished occurrence contrasts starkly with the robust intrinsic potential of RNA to multimerize through long-range base-pairing ("kissing") interactions, self-annealing of palindromic or complementary sequences, and stable tertiary contact motifs, such as the GNRA tetraloop-receptors. To explore the general mechanics of RNA dimerization, we performed a meta-analysis of a collection of exemplary RNA homodimer structures consisting of viral genomic elements, ribozymes, riboswitches, etc., encompassing both functional and fortuitous dimers. Globally, we found that domain-swapped dimers and antiparallel, head-to-tail arrangements are predominant architectural themes. Locally, we observed that the same structural motifs, interfaces and forces that enable tertiary RNA folding also drive their higher-order assemblies. These feature prominently long-range kissing loops, pseudoknots, reciprocal base intercalations and A-minor interactions. We postulate that the scarcity of functional RNA multimers and limited diversity in multimerization motifs may reflect evolutionary constraints imposed by host antiviral immune surveillance and stress sensing. A deepening mechanistic understanding of RNA multimerization is expected to facilitate investigations into RNA and RNP assemblies, condensates, and granules and enable their potential therapeutical targeting.
与生命所有领域中普遍存在的蛋白质二聚体和多聚体相比，功能 RNA 寡聚体在自然界中至今很少被观察到。它们的出现频率较低，与 RNA 通过长距离碱基配对（“亲吻”）相互作用、回文或互补序列的自身退火以及稳定的三级接触模体（如 GNRA 四联体受体）进行多聚化的强大内在潜力形成鲜明对比。为了探索 RNA 二聚化的一般机制，我们对一组由病毒基因组元件、核酶、核糖开关等组成的典型 RNA 同源二聚体结构进行了荟萃分析，其中包括功能性和偶然的二聚体。总体而言，我们发现，结构域交换二聚体和反平行、头到尾排列是主要的结构主题。在局部，我们观察到，使三级 RNA 折叠的相同结构基序、界面和力也驱动其高级组装。这些特征主要包括长距离亲吻环、假结、相互碱基插入和 A-小体相互作用。我们假设，功能性 RNA 多聚体的稀缺性和多聚化模体的有限多样性可能反映了宿主抗病毒免疫监视和应激感应施加的进化限制。对 RNA 多聚化的深入机制理解有望促进对 RNA 和 RNP 组装、凝聚体和颗粒的研究，并能够对其进行潜在的治疗靶向。
