RoL: FELS: EAGER: Connecting RNA Molecular Kinetics to Developmental Regulation

RoL：FELS：EAGER：将 RNA 分子动力学与发育调控联系起来

• 批准号: 1838345
• 负责人: Leslie Sieburth
• 金额: $ 30万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1838345&HistoricalAwards=false
• 关键词: RoL; FELS; EAGER; Connecting; RNA

Understanding how cells perceive and respond to developmental signals is critical to understanding how an organism develops its overall shape and structure. One important way that cells respond is through changes in gene expression, which is typically monitored by measuring mRNA abundance. However, changes in mRNA abundance have not been a highly predictive tool for understanding growth and development. This project will address whether specific mRNA decay characteristics improve predictive power by investigating RNA decay rates in the plant Arabidopsis thaliana in response to signals that drive development. Information learned through this study will provide deeper understanding of developmental signals and their cellular responses, which will yield better predictions of how targeted genetic changes might lead to desired traits in agriculture and medicine. Project participants will be involved in local K-12 science education. Undergraduate scientists, including those from under-represented groups, will be trained in modern molecular and cell biology techniques. This project will investigate a rule of life that high rates of RNA flux, or fast RNA turnover, provide predictive power when analyzing transcriptome data because high-flux RNAs are expected to have the fastest abundance-level response to an inductive signal. The project will follow mRNA decay rate responses to inductive signals with a focus on vascular development, an important emergent property of plants. mRNA decay rates will be analyzed genome-wide using mathematical modeling approaches to identify two mRNA decay rate parameters, flux and the beta parameter, and mRNAs whose decay rates change over the time course of vascular development. The project will test whether changes in mRNA decay rates are necessary by imposing constitutive fast or slow decay, while controlling for protein abundance, and comparing induced vascular development responses of wild type and decay-rate-modified tissues. The new experimental tool for engineering stability (or instability) into RNAs has the potential to also impact synthetic biology approaches. Elucidation of the role of RNA flux in fine control of gene expression as a rule of life might lead to better forecasting of the post-transcriptional regulatory potential of genes responsible for controlling emergent properties such as development of leaf vascular patterning.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

了解细胞如何感知和响应发育信号对于了解生物体如何发展其整体形状和结构至关重要。细胞响应的一个重要方式是通过基因表达的变化，这通常通过测量mRNA丰度来监测。然而，mRNA丰度的变化并不是理解生长和发育的高度预测工具。该项目将通过研究拟南芥中响应于驱动发育的信号的RNA衰变率来解决特定mRNA衰变特征是否提高预测能力。通过这项研究了解到的信息将提供对发育信号及其细胞反应的更深入理解，这将更好地预测有针对性的遗传变化如何导致农业和医学中所需的性状。项目参与者将参与当地的K-12科学教育。 本科科学家，包括来自代表性不足群体的科学家，将接受现代分子和细胞生物学技术的培训。该项目将研究一种生活规则，即高速率的RNA通量或快速RNA周转，在分析转录组数据时提供预测能力，因为高通量RNA预计对诱导信号具有最快的丰度水平响应。该项目将跟踪mRNA衰减率对诱导信号的反应，重点关注植物的重要紧急特性--维管发育。将使用数学建模方法在全基因组范围内分析mRNA衰减速率，以确定两个mRNA衰减速率参数，通量和β参数，以及衰减速率随血管发育时间过程变化的mRNA。该项目将测试mRNA衰变率的变化是否是必要的，通过施加组成性快速或缓慢衰变，同时控制蛋白质丰度，并比较野生型和衰变率修饰组织的诱导血管发育反应。将稳定性（或不稳定性）工程化到RNA中的新实验工具也有可能影响合成生物学方法。阐明RNA通量在精细控制基因表达中的作用，作为生活的一条规则，可能会导致更好地预测基因的转录后调控潜力，这些基因负责控制叶维管patterning.This奖项的发展等紧急属性，反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。