Molecular and Genetic Dissection of Ultraviolet-B Signaling in Arabidopsis

描述（由申请人提供）：所有暴露在阳光下的生物体都必须遇到紫外线B（UV-B，280-320 nm），这是太阳辐射的一个组成部分。根据其能量水平，UV-B对生物有机体可能有害或有益。高水平的UV-B会造成直接伤害，包括DNA损伤、白内障、皮肤癌和动物免疫系统抑制，以及植物生长迟缓和光合作用抑制。另一方面，低水平的UV-B可以提供有益的效果，包括作为植物发育的信号和帮助人类合成维生素D。也有报告指出，UV-B对人类癌症有相反的影响。虽然UV-B是一种已知的致癌物质，会导致皮肤癌，但它可以帮助抑制前列腺癌的发展。高强度UV-B辐射对生物体的损伤效应已被广泛研究，但对细胞如何感受低强度UV-B并吸收其特异性信号的分子机制知之甚少。低水平的UV-B感知和信号传导是植物中有充分记载的生理现象，但所涉及的UV-B特异性受体的分子性质仍然是难以捉摸的。了解细胞如何在各个层面感知和响应UV-B的分子机制对农业和人类健康都至关重要。由于缺乏与低水平UV-B特异性相关的明确的可筛选表型，因此很难从遗传学上确定低水平UV-B激活的特定途径。我们已经确定了一个拟南芥突变体，rus 1是特别敏感的低水平的UV-B。rus 1引人注目的表型和极端的UV-B敏感性提供了一个可行的平台，以确定遗传组件，可以是很好的候选人的UV-B特异性受体和信号组件。我们的长期目标是阐明拟南芥中低水平UV-B信号传导的分子机制。我们在本申请中的目标是表征与RUS 1在遗传和生物化学上相互作用的信号传导组分。我们的中心假设是，RUS 1及其伙伴在低水平UV-B感知中起着关键作用。我们提出了以下两个具体目标：目标1：通过定位和克隆基因外rus 1抑制基因来表征特定的UV-B信号传导组分;目标2：研究RUS 1相互作用蛋白在UV-B信号传导中的功能作用。这些研究是创新的，因为UV-B信号通路的解剖将提供细胞如何感知和响应低水平UV-B的重要信息。在这些研究完成后，我们希望了解RUS 1如何与其他组分一起响应环境低水平UV-B的分子机制。这些研究的成功完成将有助于更深入地了解细胞如何在不同水平上感知和响应UV-B，以及所学到的知识最终可用于为动物和人类开发更好的农业实践和更好的健康建议。 公共卫生相关性：紫外线-B是一种不可避免的环境因素，既可以作为人类致癌物有害，也可以作为前列腺癌抑制剂有益。虽然人们对高水平UV-B的破坏作用了解很多，但对细胞如何通过感知低水平UV-B而受益的分子机制却知之甚少。我们在这里的贡献是一个详细的分子理解拟南芥细胞如何感知和响应低水平的UV-B。这一贡献最终可用于制定更好的健康建议和加强农业实践。

DESCRIPTION (provided by applicant): All sun-exposed organisms have to encounter ultraviolet-B (UV-B, 280-320 nm), an integral part of solar radiation. Depending on its energy levels, UV-B can be harmful or beneficial to biological organisms. High- level UV-B causes direct harms including DNA damage, eye cataracts, skin cancer, and immune system suppression in animals, as well as retarded growth and depressed photosynthesis in plants. On the other hand, low-level UV-B can provide beneficial effects including serving as developmental signals in plants and aiding vitamin D synthesis in human. Opposing effects of UV-B on human cancers have also been reported. While UV-B is a known carcinogen that causes skin cancer, it can help suppress prostate cancer development. The damaging effects of high-level UV-B have been intensively studied in many organisms, but little is known about the molecular mechanism of how cells sense low-level UV-B and transduce its specific signals. Low-level UV-B perception and signaling are well-documented physiological phenomena in plants, but the molecular nature of the involved UV-B-specific receptor(s) remains elusive. Understanding the molecular mechanism of how cells sense and respond to UV-B at all levels is fundamentally important to both agriculture and human health. It has been difficult to genetically pin down a specific pathway that is activated by low-level UV-B because of the lack of unambiguous screenable phenotypes specifically associated with low-level UV-B. We have identified an Arabidopsis mutant, rus1 that is specifically hypersensitive to low- level UV-B. The striking phenotypes and extreme UV-B sensitivities of rus1 provide a feasible platform to identify genetic components that can be good candidates for UV-B specific receptors and signaling components. Our long-term goal is to delineate the molecular mechanism of low-level UV-B signaling in Arabidopsis. Our objective in this application is to characterize signaling components that genetically and biochemically interact with RUS1. Our central hypothesis is that RUS1 and its partners function as key players in low-level UV-B perception. We propose the following two specific aims: Aim 1: Characterize specific UV-B signaling components by mapping and cloning extragenic rus1 suppressor genes; Aim 2: Investigate functional roles of RUS1-interacting proteins in UV-B signaling. These studies are innovative in that the dissection of the UV-B signaling pathway would provide vital information of how cells sense and respond to low-level UV-B. At the completion of these studies we expect to know the molecular mechanism of how RUS1 works with other components to respond to environmental low-level UV-B. The successful completion of these studies will help bring a more profound understanding of how cells sense and respond to UV-B at different levels and what is learned can be ultimately used to develop enhanced agricultural practices and better health recommendations for both animals and human. PUBLIC HEALTH RELEVANCE: Ultraviolet-B, an unavoidable environmental factor, can be either harmful as a human carcinogen or beneficial as a prostate cancer suppressor. While much is known about the damaging effect of high-level UV-B, little is known about the molecular mechanism of how cells can be benefited by perceiving low-level UV-B. Our contribution here is to be a detailed molecular understanding of how Arabidopsis cells sense and respond to low-level UV-B. This contribution can be ultimately used to develop better health recommendations and enhanced agricultural practices.