Characterization of a Model System to Advance Triple-Stranded RNA Biology
推进三链 RNA 生物学的模型系统的表征
基本信息
- 批准号:10457927
- 负责人:
- 金额:$ 38.63万
- 依托单位:
- 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:2019-08-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AreaBinding ProteinsBiochemicalBiologicalBiological AssayBiological ModelsBiological ProcessBiologyCellsComplexDevelopmentDiseaseFoundationsGenesHealthHumanIn VitroInvestigationKnowledgeMALAT1 geneMalignant NeoplasmsMediatingMethodsMethyltransferaseMiller-Dieker SyndromeMolecularNatureNeurodegenerative DisordersPrincipal InvestigatorProteinsRNARNA BindingRNA DegradationRNA SplicingRNA-Binding ProteinsResearchRibonucleoproteinsRoleStructureX-Ray Crystallographybasedesigngenome editinginsightmRNA Precursornovelsmall moleculetelomeretime usetooltriple helix
项目摘要
Project Summary
Excitement about RNA triple helices has grown rapidly in recent years due to their newfound biological roles in
telomere synthesis, pre-mRNA splicing, protecting cancer-promoting RNAs from degradation and now genome
editing. Therefore, the discovery and characterization of more RNA triple helices is a pre-requisite to
elucidating other fundamental biological processes mediated by triple-helical structures. As only 11 naturally
occurring RNA triple helices have been validated to date and more are predicted, there is a clear need for the
development of molecular tools to determine the global landscape of RNA triple helices throughout nature.
Herein, the principal investigator proposes to characterize the MALAT1 (metastasis-associated lung
adenocarcinoma transcript 1) RNA triple helix and its protein-binding partner, METTL16 (methyltransferase-like
protein 16). The MALAT1 triple helix and METTL16 complex is the first putative triple-stranded
ribonucleoprotein complex, thereby representing a unique opportunity to provide unprecedented insights into
triple-stranded RNA biology. In Research Areas #1 and #2, the structural basis of how METTL16 and small
molecules specifically recognize and interact with the MALAT1 triple helix will be determined for the first time
using a combination of X-ray crystallography and biochemical methods. This effort will generate the
foundational knowledge needed to develop novel experimental tools for the global discovery of more RNA
triple helices. Moreover, the discovery of an entirely new class of proteins, that is triple-stranded RNA-binding
proteins, is anticipated. In Research Areas #3 and #4, the biological function of human METTL16 as a putative
triple-stranded RNA-binding protein will be investigated using both in vitro and cell-based biochemical assays.
This functional investigation will focus on the roles of the METTL16-MALAT1 triple helix complex as well as
broader roles for METTL16 and its RNA-binding partners in the context of Miller-Dieker Syndrome, a rare
neurodegenerative disease in which one chromosomal copy of the mettl16 gene is deleted. Thus, METTL16
and the MALAT1 triple helix represent a model system with high potential to transform the field of triple-
stranded RNA biology, opening unforeseen areas of biomedical investigation.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JESSICA Ann BROWN其他文献
JESSICA Ann BROWN的其他文献
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{{ truncateString('JESSICA Ann BROWN', 18)}}的其他基金
Characterization of a Model System to Advance Triple-Stranded RNA Biology
推进三链 RNA 生物学的模型系统的表征
- 批准号:
10669618 - 财政年份:2019
- 资助金额:
$ 38.63万 - 项目类别:
Characterization of a Model System to Advance Triple-Stranded RNA Biology
推进三链 RNA 生物学的模型系统的表征
- 批准号:
10210410 - 财政年份:2019
- 资助金额:
$ 38.63万 - 项目类别:
Characterization of a Model System to Advance Triple-Stranded RNA Biology
推进三链 RNA 生物学的模型系统的表征
- 批准号:
9797666 - 财政年份:2019
- 资助金额:
$ 38.63万 - 项目类别:
Elucidating the Inhibitory Mechanisms of RNA Triple Helices in Nuclear Decay
阐明 RNA 三螺旋在核衰变中的抑制机制
- 批准号:
9535374 - 财政年份:2014
- 资助金额:
$ 38.63万 - 项目类别:
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