Mechanisms and functions of RNA NAD+ capping and decapping

项目摘要 RNA m7 G帽已经被认为是真核生物RNA代谢的顶点，这要归功于几十年的研究。 许多研究揭示了其沉积、去除和对基因影响的机制， 表情然而，最近的发现表明，m7 G帽不是唯一的RNA帽，这表明我们的研究表明， 关于RNA代谢的知识还远未完成。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，这种帽 广泛存在于模式植物拟南芥中，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，因为存款和删除NAD+帽的酶具有 在细菌、人类和拟南芥中被发现。这种RNA修饰的潜在动态性质 指出了它在基因表达和生物过程中的未知调节功能。当NAD+服务于 在细胞氧化还原和能量稳态中起关键作用，RNA中的NAD+加帽/去帽可能是 受细胞氧化还原和代谢稳态调节并影响细胞氧化还原和代谢稳态。尽管其潜在的重要性， 我们对NAD+帽的了解最多是基本的。 该项目旨在了解使用拟南芥模型的RNA NAD+帽的生物学。基于 在初步研究中，记录了NAD+加帽RNA的存在，暗示它们的翻译 状态和揭示潜在的去帽酶，该项目询问NAD+帽如何沉积， 去除，NAD+帽如何影响基因表达，以及RNA调节哪些生物过程 NAD+-加帽/去帽。拟南芥模型中复杂的分子和遗传资源 我们不仅可以理解生命中一个领域的这种普遍的RNA修饰，而且还可以提供 在完整的多细胞生命中研究这种RNA修饰相对容易。调查结果 该项目的RNA NAD+ cap可能对农业和医学产生深远的影响。

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.