Translation regulation of gene expression in toxic dinoflagellates

有毒甲藻基因表达的翻译调控

• 批准号: 8707455
• 负责人: ROSEMARY JAGUS
• 金额: $ 12.75万
• 依托单位: CENTER FOR ENVIRONMENTAL SCIENCE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-24 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8707455
• 关键词: Affect; Affinity; Affinity Chromatography; Antibodies; Binding; Biological Assay; Biological Markers; Cell Extracts; Cells; Cellular Stress; Complementary DNA; Coupled; Databases; Development; Dinophyceae; Environment; Eukaryota; Family member; Gel; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genome; Genomics; Goals; Growth; In Vitro; Incubated; Intervention; Investigation; Length; Life; Life Cycle Stages; Light; Messenger RNA; Monitor; Mus; Neurotoxins; Organism; Parasites; Peroxides; Phase; Phosphorylation; Phosphotransferases; Physiological; Plants; Plasma; Plasmodium falciparum; Play; Policies; Polyadenylation; Process; Protein Biosynthesis; Proteins; Protista; Recombinant Proteins; Recombinants; Regulation; Research Personnel; Role; Site; Spliced Leader Sequences; Structure; Surface; Toxic effect; Toxin; Toxoplasma gondii; Trans-Splicing; Transcriptional Regulation; Translational Regulation; Translations; Variant; Yeasts; cDNA Library; eIF2 Regulation Pathway; harmful algal blooms; in vitro activity; in vivo; innovation; inorganic phosphate; insight; member; public health relevance; red tide; response; screening; sound; stressor

DESCRIPTION (provided by applicant) A number of dinoflagellate species are known to produce potent neurotoxins. Their blooms are commonly referred to as ''red tides.'' An understanding of the genetic regulatory mechanisms that affect bloom growth and, in particular, the development of biomarkers to assess bloom growth status is essential for the development of scientifically sound management and mitigation policies. The genetic organization and regulation of these organisms has been shown to be distinct from non-protist eukaryotes. Dinoflagellates are remarkable for their extremely large genomes that show little transcriptional regulation and with genes present as multiple tandem copies that are polycistronically processed through coupled trans-splicing and polyadenylation. A broad range of investigations has implicated mRNA recruitment as a major site of regulation of gene expression. However, relatively little is understood regarding translational initiation and its regulation in these organisms. The goal of this application is to unravel the roles of the likely key players in translational regulation, eIF2 and eIF4, along with the spliced leader cap structures in regulating gene expression. Using the icthyotoxic dinoflagellate, Karlodinium veneficum and the toxin producing Karenia brevis, the investigators will a) determine whether changes in eIF2-alpha phosphorylation underlie dial changes in gene expression or responses to different stressors; b) begin characterization of the eIF2-alpha-kinases from K. veneficum; c) characterize the ability of K.veneficum eIF4E family member to bind to cap structures and translational binding partners; d) assess the role of K.veneficum eIF4E members in mRNA recruitment. The investigators current understanding of translational regulation is derived mainly from studies in mouse, yeast and plants and does not allow for the diversity of eukaryotic life, the bulk of which is to be found in the Protista. The investigators' results are expected to define a new paradigm for translational regulation in dinoflagellates and represent an innovative approach to increase our understanding of the translational process itself as well as to bridge the gap between genomics and physiological complexity in dinoflagellates. Given the central role of translation in dinoflagellate gene expression, this will provide critical insight into mechanisms relevant to dinoflagellate growth, toxicity, and the regulation of harmful algal blooms.

描述（由申请人提供） 已知许多甲藻物种会产生强效神经毒素。它们的水华通常被称为“赤潮”。了解影响水华生长的遗传调控机制，特别是开发评估水华生长状态的生物标记物，对于制定科学合理的管理和缓解措施至关重要。政策。这些生物体的遗传组织和调控已被证明与非原生真核生物不同。 甲藻因其极其庞大的基因组而引人注目，这些基因组几乎没有转录调控，并且基因以多个串联拷贝的形式存在，这些拷贝通过耦合的反式剪接和多腺苷酸化进行多顺反子加工。广泛的研究表明 mRNA 募集是基因表达调控的主要位点。然而，人们对这些生物体中的翻译起始及其调控了解相对较少。该应用的目标是揭示翻译调控中可能的关键参与者 eIF2 和 eIF4 的作用，以及剪接的前导帽结构在调控基因表达中的作用。利用鱼毒甲藻、Karlodinium v​​eneficum 和产生毒素的 Karenia brevis，研究人员将 a) 确定 eIF2-α 磷酸化的变化是否是基因表达或对不同应激源反应的变化的基础； b) 开始对来自 K. veneficum 的 eIF2-α-激酶进行表征； c) 表征 K.veneficum eIF4E 家族成员结合帽结构和翻译结合配偶体的能力； d) 评估 K.veneficum eIF4E 成员在 mRNA 招募中的作用。研究人员目前对翻译调控的理解主要来自对小鼠、酵母和植物的研究，并没有考虑到真核生物的多样性，其中大部分存在于原生生物中。研究人员的结果预计将定义甲藻翻译调控的新范式，并代表一种创新方法，以增加我们对翻译过程本身的理解，并弥合甲藻基因组学和生理复杂性之间的差距。鉴于翻译在甲藻基因表达中的核心作用，这将 提供与甲藻生长、毒性和有害藻华调节相关的机制的重要见解。