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

了解细胞如何感知和响应发育信号，对于了解有机体如何发展其整体形态和结构至关重要。细胞做出反应的一个重要方式是通过基因表达的变化，这通常是通过测量mRNA丰度来监测的。然而，mRNA丰度的变化并不是了解生长和发育的高度预测工具。这个项目将通过研究植物拟南芥的RNA衰减率对驱动发育的信号的反应，来解决特定的mRNA衰减特征是否提高了预测能力。通过这项研究获得的信息将提供对发育信号及其细胞反应的更深层次的理解，这将更好地预测有针对性的基因变化可能如何导致农业和医学中所需的特征。项目参与者将参与当地的K-12科学教育。本科生科学家，包括那些来自代表不足的群体的科学家，将接受现代分子和细胞生物学技术的培训。这个项目将研究一条生命规律，即在分析转录组数据时，高速率的RNA通量或快速的RNA周转提供预测能力，因为高通量RNA预计对诱导信号具有最快的丰度水平反应。该项目将跟踪mRNA衰减率对诱导信号的反应，重点放在维管发育上，这是植物的一种重要的紧急特性。将使用数学建模方法在全基因组范围内分析信使核糖核酸的衰减率，以确定两个信使核糖核酸衰减率参数，通量和β参数，以及其衰减率随着血管发育的时间进程而变化的信使核糖核酸。该项目将测试是否有必要通过施加结构性的快速或缓慢衰退，同时控制蛋白质的丰度，并比较野生型和衰减率修饰组织的诱导血管发育反应，来测试是否有必要改变mRNA衰减率。将稳定性(或不稳定性)工程转化为RNA的新实验工具也有可能影响合成生物学方法。阐明RNA通量作为生命法则在精细控制基因表达方面的作用，可能会导致更好地预测负责控制紧急特性(如叶片维管模式的发育)的基因的转录后调节潜力。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.