Structural motifs in RNA

项目摘要 正确控制基因表达对生命至关重要。虽然在发现DNA序列和转录因子的组合作用来调节转录方面取得了重大进展，但对基因表达程序中的后续步骤知之甚少。然而，现在清楚的是，基因表达的实质性调节发生在转录后，在前mRNA剪接、RNA定位、翻译和RNA衰变中，以及在RNA通过RNA结合蛋白（RBP）、microRNA和RNA化学修饰的协调中。虽然已知许多序列基序介导转录后调控，但对控制这些基序的RNA二级结构的了解要少得多。该项目的长期目标是在全基因组范围内实现RNA的结构表征。首先，我们将应用最近开发的方法来绘制活细胞中大多数人类RNA的二级结构。其次，我们将开发方法来跟踪RNA二级结构在RNA生命周期中的命运。第三，我们将开发高通量的方法来干扰和测试RNA结构的功能。这种新技术的集成管道将使研究人员能够以前所未有的速度和准确性识别和解码基因组中的调控RNA元件。

Project Summary Proper control of gene expression is essential for life. While substantial advances have been made in the discovery of DNA sequences and transcription factors that act combinatorially to regulate transcription, much less is known about later steps in the gene expression program. Nevertheless, it is now clear that substantial regulation of gene expression occurs post-transcriptionally, in pre-mRNA splicing, RNA localization, translation, and RNA decay, and in the coordination of RNAs by RNA binding proteins (RBPs), microRNAs, and RNA chemical modifications. While many sequence motifs are known to mediate post-transcriptional regulation, RNA secondary structures that govern access to these motifs are much less well understood. The long term goal of this project is to enable structural characterization of RNAs on a genome-wide scale. First, we will apply a recently developed method to map secondary structures of most human RNAs in living cells. Second, we will develop methods to follow the fate of RNA secondary structures through the RNA life cycle. Third, we will develop high throughput methods to perturb and test functions of RNA structures. This integrated pipeline of new technologies will enable investigators to identify and decode regulatory RNA elements in the genome with unprecedented speed and accuracy.