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Molecular Mechanisms in Reovirus mRNA Synthesis

呼肠孤病毒 mRNA 合成的分子机制

基本信息

批准号：
7019129
负责人：
MAX L. NIBERT
金额：
$ 33.59万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-03-10 至 2008-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7019129
关键词：
RNA binding protein RNA biosynthesis Reoviridae cryoelectron microscopy genetic transcription intracellular transport messenger RNA posttranscriptional RNA processing protein structure function recombinant proteins virus RNA virus assembly virus genetics virus protein

项目摘要

DESCRIPTION (provided by applicant): The molecular mechanisms by which mammalian orthoreoviruses (reoviruses) and other dsRNA viruses mediate synthesis of their mRNA molecules using virally encoded enzymes packaged within infectious virus particles is a subject of active inquiry because they promise insight into how the steps in mRNA synthesis - plus-strand RNA synthesis (transcription), RNA 5' capping, and RNA transport - occur within the delimited three-dimensional setting of the icosahedral virus particle. A better understanding of these mechanisms in dsRNA viruses should be useful for understanding how related processes are mediated by analogous other viral, microbial, or cellular enzymes and for designing new antiviral, antimicrobial, or anticellular agents directed at them. The long-term objective of our work with reoviruses is to define structure-function relationships for the roles of reovirus proteins in viral replication and effects on host cells and animals. In the current proposal, emphasis is placed on the proteins within the reovirus core (subviral) particle that mediates mRNA synthesis in vitro. Three specific aims are identified, which reflect where further progress appears most promising or necessary to advance understanding in this system. These aims are (1) to determine the structure of the reovirus transcriptase complexes and their arrangement in cores, (2) to define the assembly pathway of the reovirus core shell, and (3) to dissect the functions of the reovirus core proteins in RNA synthesis, capping, and transport. Reovirus particles reconstituted from recombinant proteins expressed using baculovirus vectors play a prominent role in the proposed experiments because of their broad applicability to studies of particle structure, assembly, and functions. Recently determined crystal structures of the transcription- and capping-competent reovirus core particle and the reovirus RNA-dependent RNA polymerase also figure heavily in this proposal by having focused attention on particular areas where more structure information is needed, suggested specific new hypotheses about steps in mRNA synthesis and assembly, and identified specific amino acids in the core proteins to subject to mutagenesis for structure-function testing. The results of these studies will enhance our understanding of the reovirus core as an elegantly designed molecular machine for mRNA synthesis.

描述（由申请人提供）：通过的分子机制

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）

Effects of viscogens on RNA transcription inside reovirus particles.

viscogen 对呼肠孤病毒颗粒内 RNA 转录的影响。

DOI：
10.1074/jbc.m111.241703
发表时间：
2011
期刊：
The Journal of biological chemistry
影响因子：
0
作者：
Demidenko,AleksanderA;Lee,Jinkee;Powers,ThomasR;Nibert,MaxL
通讯作者：
Nibert,MaxL

Mechanism for coordinated RNA packaging and genome replication by rotavirus polymerase VP1.

DOI：
10.1016/j.str.2008.09.006
发表时间：
2008-11-12
期刊：
Structure (London, England : 1993)
影响因子：
0
作者：
Lu X;McDonald SM;Tortorici MA;Tao YJ;Vasquez-Del Carpio R;Nibert ML;Patton JT;Harrison SC
通讯作者：
Harrison SC

Silencing and complementation of reovirus core protein mu2: functional correlations with mu2-microtubule association and differences between virus- and plasmid-derived mu2.

呼肠孤病毒核心蛋白 mu2 的沉默和互补：与 mu2-微管关联的功能相关性以及病毒和质粒衍生的 mu2 之间的差异。