Understand the function of the MOS4-associated complex in microRNA biogenesis

了解 MOS4 相关复合物在 microRNA 生物发生中的功能

基本信息

批准号：
10458618
负责人：
Bin Yu
金额：
$ 31.41万
依托单位：
UNIVERSITY OF NEBRASKA LINCOLN
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10458618
关键词：
Affect Agriculture Angiosperms Arabidopsis Binding Biogenesis Biological Models Biological Process Complex DNA Polymerase II DNA Repair DNA-Binding Proteins DNA-Directed RNA Polymerase Defect Development Diagnostic Disease Failure Family Gene Expression Gene Expression Regulation Genes Genetic Transcription Genome Stability Goals Health Human Immunity Individual Lead Ligase Link Mediating Messenger RNA Metabolism MicroRNAs Mouse-ear Cress Mustard Nuclear Nuclear RNA Organism Orthologous Gene Outcome Phosphorylation Physiology Plants Polyubiquitination Process Proteins Quality Control RNA Splicing RNA-Binding Proteins Regulation Regulator Genes Repression Research Role Spliceosomes Structure System Technology Testing Text Therapeutic Transcript Transcription Process Untranslated RNA Work Yeasts fungus improved poly A specific exoribonuclease promoter recruit stem trait ubiquitin ligase ubiquitin-protein ligase

项目摘要

Project Summary Multicellular organisms encode small non-coding RNAs called microRNAs (miRNAs) to regulate gene expression by exerting repression on their target mRNAs. Defective synthesis of miRNAs and abnormal miRNA activity are associated with developmental defects and diseases, including human. Thus, miRNAs are being targeted or used for both diagnostic and therapeutic purposes. However, there are several critical caps in miRNA biogenesis. Our long-term goal is to elucidate how miRNA levels are precisely controlled. miRNAs are derived from the primary miRNA transcripts (pri-miRNAs), which contain one or more imperfect stem-loop (s) where miRNAs reside. Pri-miRNAs are co-transcriptionally processed. However, it is not clear how the processing complex is formed and recruited to pri-miRNAs. Moreover, most pri-miRNAs are non-coding RNAs, and therefore, are likely targets of the nuclear RNA quality control machinery (QC). Indeed, failure to protect pri-miRNA from degradation causes development defects. However, the process protecting pri-miRNA from degradation is not defined. The MOS4-assoicated complex (MAC) from plants is a conserved complex composed of core and accessory components. The ortholog complexes of MAC in metazoan and fungi are known as the PRP19 complex and the nineteen complex, respectively. They associate with spliceosome and are required for splicing, DNA damage repair and genome stability. Our previous study leads us to propose that MAC links pri- miRNA transcription, processing and stability together. We hypothesize is that MAC is important for co- transcriptional processing and stability of pri-miRNAs. Our specific aims will test the following hypotheses: 1) MAC functions as a whole complex to modulate miRNA biogenesis; 2) MAC binds pri-miRNAs to protect them from XRN2/3 activity; 3) Phosphorylation-dependent ubiquitin ligase activity of MAC3 is critical for miRNA biogenesis. Collectively, our research will produce a broad impact by characterizing the roles of MAC in the transcription of pri-miRNAs, formation of processing complex, stabilization of pri-miRNAs and regulation of the activity of processing complex. Consequently, our research will improve our ability to understand the miRNA- mediated gene regulation and to develop miRNA-related technologies that can be used to improve human health and agricultural trait of crops

项目摘要多细胞生物编码称为microRNA（miRNA）的小型非编码RNA来调节基因通过在其目标mRNA上施加抑制来表达。 miRNA和异常的缺陷合成 miRNA活性与包括人在内的发育缺陷和疾病有关。因此，miRNA是被针对或用于诊断和治疗目的。但是，有几个关键的帽子在miRNA生物发生中。我们的长期目标是阐明如何精确控制miRNA水平。 miRNA源自主要miRNA转录本（PRI-MIRNA），其中包含一个或多个 miRNA居住的不完美的茎环。 Pri-MirNA是共同处理的。但是，是尚不清楚如何形成和招募加工复合物。而且，大多数pri-mirnas是非编码RNA，因此可能是核RNA质量控制机制（QC）的靶标。的确，未能保护Pri-miRNA免受降解会导致发育缺陷。但是，该过程保护未定义降解中的pri-miRNA。来自植物的MOS4分配的复合物（MAC）是由核心和附件组件。 MAC和真菌中Mac的直系同源物种被称为PRP19 复杂和十九个复合物。他们与剪接体相关，是必需的剪接，DNA损伤修复和基因组稳定性。我们以前的研究使我们提出MAC链接 miRNA转录，处理和稳定性。我们假设MAC对于共同 PRI-MIRNA的转录处理和稳定性。我们的具体目的将检验以下假设：1） MAC充当整个复合物来调节miRNA生物发生。 2）MAC绑定Pri-mirnas以保护它们来自XRN2/3活动； 3）MAC3的磷酸化依赖性泛素连接酶活性对于miRNA至关重要生物发生。总的来说，我们的研究将通过表征Mac在 PRI-MIRNA的转录，加工复合物的形成，PRI-MIRNA的稳定和调节加工复合物的活性。因此，我们的研究将提高我们了解miRNA的能力介导的基因调节并开发可用于改善人类的miRNA相关技术农作物的健康和农业特征

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

JANUS, a spliceosome-associated protein, promotes miRNA biogenesis in Arabidopsis.

DOI：
10.1093/nar/gkad1105
发表时间：
2024-01-11
期刊：
Nucleic acids research
影响因子：
14.9
作者：
通讯作者：

Alternative splicing of DSP1 enhances snRNA accumulation by promoting transcription termination and recycle of the processing complex.

DSP1 的选择性剪接通过促进转录终止和加工复合物的循环来增强 snRNA 的积累。

DOI：
10.1073/pnas.2002115117
发表时间：
2020
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Wang Weili;Pu Xuepiao;Yang Siyu;Feng Yujie;Lin Chan;Li Mu;Li Xi;Li Huali;Meng Chunmei;Xie Qingjun;Yu Bin;Liu Yunfeng
通讯作者：
Liu Yunfeng

DSP1 and DSP4 act synergistically in snRNA 3' end maturation and pollen growth

DOI：
10.1104/pp.19.00231
发表时间：
2019
期刊：
Plant Physiology
影响因子：
7.4
作者：
Xuepiao Pu;Chunmei Meng;Weili Wang;Siyu Yang;Yuan Chen;Qingjun Xie;Bin Yu;Yunfeng Liu
通讯作者：
Yunfeng Liu

Mapping of transgenic alleles in soybean using a nanopore-based sequencing strategy

使用基于纳米孔的测序策略绘制大豆转基因等位基因图谱。