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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：
9905546
负责人：
Xiuren Zhang
金额：
$ 28.94万
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 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9905546
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 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成分的作用