Mechanisms and functions of RNA NAD+ capping and decapping

项目总结 几十年来，rna m7g帽被认为是真核生物rna新陈代谢的顶峰。 揭示其沉积、去除和对基因影响的机制的研究 表情。然而，最近的发现表明，m7G帽并不是唯一的RNA帽，这表明我们的 关于RNA新陈代谢的知识还远远不完整。烟酰胺腺嘌呤二磷酸(NAD+)最近 在细菌、酵母和人类中以RNA帽的形式出现，我们的初步研究表明，这个帽是 在模式植物拟南芥中广泛存在；因此，NAD+可能是生命中普遍存在的RNA帽。现有证据 指出了这种RNA修饰的动态性质，因为沉积和去除NAD+帽的酶具有 已在细菌、人类和拟南芥中发现。这种RNA修饰的潜在动态性质 指出其在基因表达和生物过程中的调节功能尚不清楚。作为NAD+服务 在细胞氧化还原和能量动态平衡中的关键作用，有可能在RNA中NAD+封顶/解帽 受细胞氧化还原和代谢动态平衡的调节和影响。尽管它具有潜在的重要性， 我们对NAD+上限的了解至多是初级的。 该项目试图利用拟南芥模型来了解RNA NAD+CAP的生物学。基座 关于证明存在NAD+封顶的RNA的初步研究，暗示它们的翻译 状态和揭示的潜在脱帽酶，该项目询问NAD+帽是如何沉积的，以及 去除，NAD+CAP如何影响基因表达，以及哪些生物学过程受RNA调控 NAD+-封顶/解封。拟南芥模型中复杂的分子和遗传资源不是 不仅允许在生命的一个领域理解这种普遍的RNA修饰，而且还提供了 相对容易地在完整的多细胞生命中研究这种RNA修饰的优势。调查结果： 来自该项目的RNA NAD+CAP可能对农业和医药产生深远影响。

PROJECT SUMMARY The RNA m7G cap has been recognized as a capstone in RNA metabolism in eukaryotes, thanks to decades of research that uncovered the mechanisms underlying its deposition, removal, and impacts on gene expression. However, recent discoveries showing that the m7G cap is not the only RNA cap indicate that our knowledge of RNA metabolism is far from complete. Nicotinamide adenine diphosphate (NAD+) has recently emerged as an RNA cap in bacteria, yeast, and humans, and our preliminary studies show that this cap is widespread in the model plant Arabidopsis; thus, NAD+ maybe a universal RNA cap in life. Existing evidence points to a dynamic nature of this RNA modification, as enzymes that deposit and remove the NAD+ cap have been identified in bacteria, humans, and Arabidopsis. The potentially dynamic nature of this RNA modification points to its as yet unknown regulatory functions in gene expression and biological processes. As NAD+ serves critical functions in cellular redox and energy homeostasis, it is possible that NAD+ capping/decapping in RNA is both regulated by and impacts cellular redox and metabolic homeostasis. Despite its potential importance, our knowledge of the NAD+ cap is at most rudimentary. The project seeks to understand the biology of the RNA NAD+ cap using the Arabidopsis model. Based on preliminary studies that documented the existence of NAD+-capped RNAs, implicated their translational status and revealed potential decapping enzymes, the project interrogates how the NAD+ cap is deposited and removed, how the NAD+ cap impacts gene expression, and what biological processes are regulated by RNA NAD+-capping/decapping. The sophisticated molecular and genetic resources in the Arabidopsis model not only allow for the understanding of this universal RNA modification in one domain of life, but also offer advantages of studying this RNA modification in an intact, multicellular life with relative ease. Findings on the RNA NAD+ cap from this project may have far-reaching impacts in agriculture and medicine.