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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小的非编码RNA，称为microRNA（miRNAs），通过对它们的靶mRNA施加抑制来表达。miRNAs合成缺陷和异常 miRNA活性与发育缺陷和疾病相关，包括人类。因此，作为诊断和治疗目的的目标或用于诊断和治疗目的。然而，有几个关键的上限，在miRNA的生物发生中。我们的长期目标是阐明如何精确控制miRNA水平。 miRNA来源于初级miRNA转录物（pri-miRNA），其含有一个或多个miRNA转录物，不完美的茎-环，其中存在miRNA。Pri-miRNA是共转录加工的。但据目前尚不清楚加工复合物是如何形成和募集到pri-miRNAs的。此外，大多数pri-miRNAs 因此，非编码RNA可能是核RNA质量控制机制（QC）的目标。的确，不能保护pri-miRNA免于降解导致发育缺陷。然而，保护过程未定义降解产生的pri-miRNA。来自植物的MOS 4-assoicated complex（MAC）是一种保守的复合物，附件组件。MAC在后生动物和真菌中的直向同源复合物被称为PRP 19 复体和十九复体。它们与剪接体相关，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链路pri- miRNA的转录、加工和稳定性。我们假设MAC对于共同- pri-miRNAs的转录加工和稳定性。我们的具体目标将测试以下假设：1） MAC作为一个整体复合物来调节miRNA的生物合成; 2）MAC结合pri-miRNAs来保护它们 3）磷酸化依赖性的泛素连接酶活性对于miRNA的表达至关重要。生物起源总的来说，我们的研究将通过描述MAC在 pri-miRNAs的转录，加工复合物的形成，pri-miRNAs的稳定化和处理复杂的活动。因此，我们的研究将提高我们理解miRNA的能力- 介导的基因调控，并开发可用于改善人类健康的miRNA相关技术。作物健康和农业性状

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。