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Roles of SWI/SNF complexes in posttranscriptional processing of RNA

SWI/SNF 复合物在 RNA 转录后加工中的作用

基本信息

批准号：
10355465
负责人：
Xiuren Zhang
金额：
$ 29.85万
依托单位：
TEXAS A&M AGRILIFE RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-02 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10355465
关键词：
ATP Hydrolysis ATP phosphohydrolase Address Agriculture Animal Model Arabidopsis Architecture Binding Biogenesis Biological Assay Biological Process Biology Biotechnology Cell Nucleus Chromatin Chromatin Remodeling Factor Chromatin Structure Code Complex DNA Defect Disease Eukaryota Functional disorder Gene Expression Genetic Transcription Goals Health Human Immunoprecipitation Malignant Neoplasms Mediating Messenger RNA MicroRNAs Microprocessor Mitochondria Modification Molecular Morphology Multiplexed Analysis of Projections by Sequencing Mutagenesis Mutation Names Nucleosomes Orthologous Gene Pathway interactions Pharmacologic Substance Phenocopy Phenotype Physiological Plastids Play Post-Transcriptional RNA Processing Process Production Proteins Proteomics RNA RNA Editing RNA Processing RNA Splicing Research Ribonucleoproteins Role SWI2/SNF2 Secure Series Small RNA Structure Sucrose Testing Therapeutic Transcript Translations Untranslated RNA Variant Yeasts chromatin remodeling cofactor dimethyl sulfide gene function gene regulatory network genome-wide human disease improved in vivo knock-down loss of function mRNA Precursor messenger ribonucleoprotein mutant novel pri-miRNA protein complex trait transcriptome transcriptome sequencing

项目摘要

The primary goal of the proposed research is to determine the roles of SWI/SNF component CHR2/BRM ATPase in posttranscriptional processing of RNA transcriptome. CHR2/BRM is the ATPase subunit of the large SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complexes. SWI/SNF complexes are best known to remodel chromatin structures using energy derived from ATP hydrolysis. Metazoan and yeast SWI/SNF complexes also associate with nascent mRNA ribonucleoprotein complexes and long-noncoding RNAs (lncRNAs). All these studies suggest that CHR2 and other SWI/SNF factors play non-canonical roles in RNA biology. Whether and how SWI/SNF components directly participate in post- transcriptional processing of RNA are unknown. Once thought to be only a messenger bridge between DNA and proteins, RNA is now known to influence many aspects of biology through activities that are attributable to its secondary structures. In fact, RNA secondary structures (RSS) contain a new set of information code that is interpreted and processed by specialized protein complexes to regulate RNA transcription, splicing, translation, localization and turnover. However, little is known about the identities of the proteins/complexes that can recognize specific target RNAs; and how they promote the structural remodeling of RSS in vivo. Many RNA species also undertake posttranscriptional RNA editing and /or modifications (REMs), which even add more complexity to regulate gene expression and biological functions. Whether and how RSS remodeling and REM alternation crosstalk with each other in higher eukaryotes, especially in the nucleus, is underexplored. The PI Zhang has recently made a groundbreaking discovery that CHR2 could remodel primary precursors of microRNAs and inhibit their processing in the model organism Arabidopsis. In the preliminary study, CHR2 was also found to have a cofactor named as multiple organellar RNA editing factor 8 (MORF8). MORF8 typically functions in mitochondria and plastids to participate in REMs. Importantly, loss-of-function mutants of CHR2 and MORF8 share nearly identical molecular and morphological defects in the microRNA pathway. In this setting, the PI Zhang would like to systematically investigate the roles of CHR2 in posttranscriptional processing of various RNA transcripts. Specifically, The PI Zhang proposes to: 1) identify the CHR2-bound mRNAs and lncRNAs among others and determine how CHR2 alters the RSS of transcriptome at the genome- wide level; and 2) conduct functional analysis of MORF8 in the nucleus; and determine whether and how CHR2-controlled RSS remodeling and MORF8-regulated REMs interplay with each other to control gene expression and functions. The proposed study will reveal the non-canonical but increasingly important roles of SWI/SNF complexes in posttranscriptional processing of RNA molecules. The new functions of SWI/SNF in RNA biology may be exploited in biotechnological and pharmaceutical applications to address physiological disorders that arise from dysfunctions of RNA processing in eukaryotes including human. !

本研究的主要目的是确定SWI/SNF组件的作用 CHR2/BRM ATP酶在RNA转录组转录后加工中的作用CHR2/BRM是ATP酶 SWITCH/蔗糖非发酵（SWI/SNF）染色质重塑复合物的大亚基。SWI/SNF 最为人所知的是，复合物利用来自ATP水解的能量来重塑染色质结构。后生动物和酵母SWI/SNF复合物也与新生mRNA核糖核蛋白复合物结合和长链非编码RNA（lncRNA）。所有这些研究都表明CHR2和其他SWI/SNF因子发挥作用， RNA生物学中的非规范角色。SWI/SNF各组成部分是否以及如何直接参与 RNA的转录过程是未知的。曾经被认为只是DNA之间的信使桥梁和蛋白质，RNA现在已知通过可归因于以下的活动影响生物学的许多方面：它的二级结构。事实上，RNA二级结构（RSS）包含一组新的信息代码，由专门的蛋白质复合物解释和加工，以调节RNA转录、剪接、翻译，本地化和营业额。然而，很少有人知道蛋白质/复合物的身份，识别特定的靶RNA;以及它们如何促进体内RSS的结构重塑。许多rna 物种还进行转录后RNA编辑和/或修饰（REM），这甚至增加了更多的复杂性来调节基因表达和生物学功能。是否以及如何RSS重塑和REM 高等真核生物中，尤其是细胞核中的交替串扰尚未得到充分研究。的pi Zhang最近取得了一项突破性的发现，CHR2可以重塑在模式生物拟南芥中，microRNA和抑制它们的加工。在初步研究中，另外还发现有一个辅助因子，命名为多细胞器RNA编辑因子8（MORF 8）。MORF 8通常在线粒体和质体中起作用以参与REM。重要的是，CHR2的功能丧失突变体和MORF8在microRNA途径中具有几乎相同的分子和形态缺陷。在这在此背景下，张毅希望系统地研究CHR2在转录后调控中的作用，各种RNA转录物的加工。具体而言，PI Zhang建议：1）确定CHR2结合的 mRNA和lncRNA等，并确定CHR2如何改变基因组转录组的RSS- 2）对MORF 8在细胞核中的功能进行分析，并确定其是否以及如何表达。 CHR2控制的RSS重塑和MORF8调节的REM相互作用以控制基因表达。表达和功能。这项拟议的研究将揭示非典型但日益重要的作用， RNA分子转录后加工中的SWI/SNF复合物。SWI/SNF的新功能 RNA生物学可用于生物技术和制药应用，以解决生理学问题。由真核生物（包括人类）中RNA加工功能障碍引起的疾病。 !

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

HASTY moves to chromatin for miRNA production.

DOI：
10.1016/j.molp.2021.01.012
发表时间：
2021-03-01
期刊：
Molecular plant
影响因子：
27.5
作者：
Sun D;Zhang X
通讯作者：
Zhang X

Identification and Quantification of Small RNAs.

DOI：
10.1007/978-1-0716-0880-7_11
发表时间：
2021
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
0
作者：
Sun D;Ma Z;Zhu J;Zhang X
通讯作者：
Zhang X

PRP4KA phosphorylates SERRATE for degradation via 20S proteasome to fine-tune miRNA production in Arabidopsis.

DOI：
10.1126/sciadv.abm8435
发表时间：
2022-03-25
期刊：
Science advances
影响因子：
13.6
作者：
Wang L;Yan X;Li Y;Wang Z;Chhajed S;Shang B;Wang Z;Choi SW;Zhao H;Chen S;Zhang X
通讯作者：
Zhang X

Structured 3′ UTRs destabilize mRNAs in plants