Role of ROP GTPases in sulfate transceptor SULTR1;2-regulated sulfur nutrient sensing

ROP GTPases 在硫酸盐受体 SULTR1;2 调节的硫营养物传感中的作用

• 批准号: 10666554
• 负责人: ZHI-LIANG ZHENG
• 金额: $ 14.51万
• 依托单位: HERBERT H. LEHMAN COLLEGE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666554
• 关键词: Alleles; Amino Acids; Arabidopsis; Binding; Biochemical; C-terminal; Cell Nucleus; Cell membrane; Cells; Code; Complex; Cytoplasm; Disease; Drug Targeting; Elements; Enhancers; Environment; Eukaryota; Event; FHL1 gene; Family; Gene Expression; Genes; Genetic; Genetic Transcription; Goals; Growth and Development function; Guanosine Triphosphate Phosphohydrolases; Human; Lead; Link; MAP Kinase Modules; Malignant Neoplasms; Measures; Mediating; Micronutrients; Minerals; Modeling; Modification; Monomeric GTP-Binding Proteins; Nitrates; Nutrient; Organism; Pathologic; Pathway interactions; Pattern; Peptides; Phenotype; Phosphoric Monoester Hydrolases; Phosphorylation; Physiological; Plant Model; Plants; Polymerase; Post-Translational Protein Processing; Productivity; Proteins; RNA Polymerase II; RNA polymerase II largest subunit; Regulatory Element; Reporting; Research; Role; Signal Transduction; Sulfate; Sulfur; System; Testing; Transcription Initiation; Transcriptional Regulation; Work; Yeasts; Zinc; detection of nutrient; drug development; fungus; gain of function; improved; inorganic phosphate; insight; loss of function; member; mutant; novel; nutrition; promoter; protein degradation; protein function; public health relevance; receptor; recruit; response; rho; rho GTP-Binding Proteins; sensor; sulfate transporter; transcription factor; transcription factor TFIIH; uptake

ABSTRACT Many living organisms including humans have evolved mechanisms to sense and respond to levels of mineral nutrients or amino acids. In this application, we propose to use Arabidopsis plant sulfur (S) nutrient sensing and signaling as an experimental system to dissect transporting receptor-mediated nutrient sensing mechanisms. Our prior research has led to identification of sulfate transporter SULTR1;2 as a receptor. This type of dual-function transporting receptor, termed transceptor, has been increasingly found in eukaryotic organisms and is expected to increase nutrient use efficiency by performing both its sensing and transporting functions. However, how plants use the transceptor SULTR1;2 to transduce the S signal in the control of gene expression has remained a central unanswered question and becomes the focus of the present project. Our recent studies have revealed a conserved shortcut model of transcriptional control that links Rho family small GTPases to RNA polymerase II (Pol II) C-terminal domain (CTD) Ser phosphorylation across plants, fungi and humans. The Pol II CTD contains various number of conserved heptad peptide repeats (Y1S2P3T4S5P6S7) in which each amino acid can be subjected to different posttranslational modifications. Thus, the posttranslational modification pattern is complex and collectively called the CTD code. Among the CTD code, Ser2 and Ser5 phosphorylation along the gene is very important for initiating transcription and completing the transcription cycle. In the classical model of transcriptional control, upon activation by Rho or Ras GTPases, the MAP kinase cascade activates transcription factors that bind to gene-specific cis-elements and helps recruit Pol II to the core promoter. In contrast, in the shortcut model, Rho GTPase signaling directly targets the Pol II CTD Ser2 and Ser5 phosphorylation and thus can rapidly bring about large-scale gene expression changes. We now have preliminary evidence indicating that activity of ROP2 GTPase, which is a member of plant-unique ROP subfamily of Rho GTPases, and levels of CTD Ser2 and Ser5 phosphorylation are impacted by S status. In addition, ROP GTPase activity is higher in SULTR1;2 mutants. Therefore, we hypothesize that ROP2 and its functionally redundant ROP4 act as negative regulators in SULTR1;2-mediated S sensing and signaling. The proposed work aims to fill the major gaps from SULTR1;2 to Pol II transcription. Specifically, Aim 1 is to test that ROP2 and ROP4 GTPases act as negative regulators in SULTR1;2-mediated S sensing and signaling using genetic and biochemical approaches. Aim 2 is to test the hypothesis that ROP2-mediated Pol II shortcut model is required for S response. In Aim 3, we propose to test that ROP2-controlled SLIM1 transcription factor activity and ROP2-mediated Pol II CTD code modulation act cooperatively to achieve the most productive transcription of S-deficiency induced S-response genes. The proposed study will not only lead to novel mechanistic insights into how plants use nutrient transceptor SULTR1;2 and ROP signaling switch to efficiently control gene expression but also provide a paradigm for transcriptional regulation in other organisms.

摘要