Structural motifs in RNA

RNA 中的结构基序

• 批准号: 9474334
• 负责人: Howard Y Chang
• 金额: $ 3.33万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9474334
• 关键词: 3' Untranslated Regions; Acylation; Address; Adopted; Base Pairing; Binding Sites; Biochemical; Biochemical Genetics; Biological Assay; Biological Process; Biotechnology; Cell Nucleus; Cells; Chemicals; Chromatin; Cytoplasm; DNA Sequence; Data; Disease; Elements; Frequencies; Gene Expression; Gene Expression Regulation; Genes; Genetic Medicine; Genetic Transcription; Genetic screening method; Genome; Germ Layers; Goals; Health; Heart; Human; Hydroxyl Radical; In Vitro; Lead; Life; Life Cycle Stages; Maps; Measures; Mediating; Messenger RNA; Methods; MicroRNAs; Modification; Molecular Conformation; Nature; Nucleic Acids; Nucleotides; Polyribosomes; Post-Transcriptional Regulation; RNA; RNA Conformation; RNA Decay; RNA Splicing; RNA Transport; RNA-Binding Proteins; Regulation; Reporter Genes; Research Personnel; Resolution; Resources; Shapes; Site; Speed; Structure; Structure-Activity Relationship; Testing; Time; Translating; Translations; Untranslated RNA; Variant; base; cell type; combinatorial; experimental study; genome-wide; high throughput technology; human disease; improved; in vivo; insight; mRNA Precursor; new technology; programs; tool; transcription factor; transcriptome

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.

项目概要 正确控制基因表达对于生命至关重要。虽然在发现组合作用调节转录的 DNA 序列和转录因子方面已经取得了实质性进展，但对基因表达程序的后续步骤知之甚少。然而，现在很清楚，基因表达的实质性调控发生在转录后，在前 mRNA 剪接、RNA 定位、翻译和 RNA 衰减中，以及在 RNA 结合蛋白 (RBP)、microRNA 和 RNA 与 RNA 的协调中。化学修饰。虽然已知许多序列基序可介导转录后调控，但控制这些基序访问的 RNA 二级结构尚不清楚。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 二级结构在整个 RNA 生命周期中的命运。第三，我们将开发高通量方法来干扰和测试 RNA 结构的功能。这种集成的新技术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。

项目成果

Tandem stem-loops in roX RNAs act together to mediate X chromosome dosage compensation in Drosophila.

roX RNA 中的串联茎环共同作用，介导果蝇中的 X 染色体剂量补偿。

• DOI: 10.1016/j.molcel.2013.07.001
• 发表时间: 2013-07-25
• 期刊: Molecular cell
• 影响因子: 16
• 作者: Ilik IA;Quinn JJ;Georgiev P;Tavares-Cadete F;Maticzka D;Toscano S;Wan Y;Spitale RC;Luscombe N;Backofen R;Chang HY;Akhtar A
• 通讯作者: Akhtar A

Transient transcriptional responses to stress are generated by opposing effects of mRNA production and degradation.

对应激的瞬时转录反应是由 mRNA 生成和降解的相反作用产生的。

• 发表时间: 2008
• 影响因子: 9.9
• 作者: Shalem, Ophir;Dahan, Orna;Levo, Michal;Martinez, Maria Rodriguez;Furman, Itay;Segal, Eran;Pilpel, Yitzhak
• 通讯作者: Pilpel, Yitzhak

Genome-wide measurement of RNA secondary structure in yeast.

酵母 RNA 二级结构的全基因组测量。

• 发表时间: 2010-09-02
• 影响因子: 64.8
• 作者: Kertesz, Michael;Wan, Yue;Mazor, Elad;Rinn, John L;Nutter, Robert C;Chang, Howard Y;Segal, Eran
• 通讯作者: Segal, Eran

Genome-wide mapping of RNA structure using nuclease digestion and high-throughput sequencing.

使用核酸酶消化和高通量测序绘制全基因组 RNA 结构图。

• 发表时间: 2013-05
• 影响因子: 14.8
• 作者: Wan, Yue;Qu, Kun;Ouyang, Zhengqing;Chang, Howard Y
• 通讯作者: Chang, Howard Y

The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline.

保守的 RNA 解旋酶 YTHDC2 调节种系从增殖到分化的转变。

• 发表时间: 2017-10-31
• 影响因子: 7.7
• 作者: Bailey, Alexis S;Batista, Pedro J;Gold, Rebecca S;Chen, Y Grace;de Rooij, Dirk G;Chang, Howard Y;Fuller, Margaret T
• 通讯作者: Fuller, Margaret T