Targets and functions of the mammalian snoRNAome
哺乳动物 snoRNAome 的目标和功能
基本信息
- 批准号:10565187
- 负责人:
- 金额:$ 77.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-22 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAntisense OligonucleotidesBindingBinding SitesBiological ProcessBiologyCell LineCellsComplexGene ExpressionGene Expression RegulationGenesGenetic TranslationGuide RNAHumanHuman GenomeIndividualInvestigationKnowledgeMapsMessenger RNAMethodsModificationMusMutationNucleotidesOrphanPathway interactionsProteinsPseudouridineRNARNA BindingRNA SplicingRNA-Binding ProteinsRegulationResearchResolutionRibonucleoproteinsRibosomal RNARibosomesRoleSmall Nucleolar RNASmall Nucleolar RibonucleoproteinsStressTechnologyTimeTissuesTranslationsUntranslated RNAbasebiological systemsbisulfitecell typehuman diseaseinventionkethoxalknock-downmRNA PrecursormRNA Stabilitynanoporenovel sequencing technologynovel strategiesprotein complexresponsetooltranscriptometranscriptomics
项目摘要
Project Abstract:
Small nucleolar RNA (snoRNA) are natural guide non-coding RNAs derived from over 900 annotated snoRNA
genes in the human genome. The major known function of about one-third of snoRNAs is to install 2’O-methyl
and pseudouridine modifications in the ribosomal RNA. These rRNA modifications guide ribosome assembly
and maturation, and fine-tune translation in a cell type and cell state dependent manner. However, the majority
of snoRNAs do not have a well described function; they are called orphans because their cellular RNA targets
are not known. How snoRNA interacts with the human transcriptome and the functional consequences of these
potential non-canonical snoRNA-RNA interactions in gene expression regulation and human diseases remain to
be determined. We recently developed several new sequencing technologies that are directly relevant to
studying snoRNA biology. They include methods to robustly identify inter-molecular RNA-RNA interactions in
cells and transcriptome-wide sequencing of 2’O-methyl and pseudouridine modifications. These new tools will
allow us to address mysteries of snoRNA biology. Aim 1 will identify the cellular RNA targets of the snoRNAome
through an advanced version of kethoxal-assisted RNA-RNA interaction sequencing (KARR-seq) approach to
enable comprehensive capture and identification of snoRNA-RNA interactions at the transcriptomic scale. These
results will be used to identify the rules of snoRNA-guided targeting of mRNA sequences. Aim 2 will investigate
two types of snoRNA-mRNA interactions transcriptome-wide and the consequences on regulating gene
expression through the application of new sequencing methods to map 2’O-methyl and pseudouridine
modifications in pre-mRNA and mature mRNA, and associate these results with the snoRNA-mRNA interactome.
We will also selectively delete snoRNA genes or knockdown snoRNA levels, alter the expression of snoRNP
components to investigate the consequence of specific snoRNA-mRNA interaction. All together these results will
provide the first comprehensive snoRNA-RNA interactome and derive the guiding principles of snoRNA-mRNA
interactions and the associated biological functions.
项目摘要:
小核仁RNA(snoRNA)是从900多种已标记的snoRNA中分离出来的天然非编码RNA
人类基因组中的基因大约三分之一的snoRNA的主要已知功能是安装2 'O-甲基
和核糖体RNA中的假尿苷修饰。这些rRNA修饰引导核糖体组装
和成熟,并以细胞类型和细胞状态依赖性方式微调翻译。但是大部分
的snoRNA没有一个很好的描述功能;他们被称为孤儿,因为他们的细胞RNA目标
不知道。snoRNA如何与人类转录组相互作用以及这些相互作用的功能后果
在基因表达调控和人类疾病中潜在的非经典snoRNA-RNA相互作用仍然存在,
被确定。我们最近开发了几种新的测序技术,
研究snoRNA生物学。它们包括稳健地鉴定分子间RNA-RNA相互作用的方法,
细胞和2 'O-甲基和假尿苷修饰的全转录组测序。这些新工具将
让我们能够解开snoRNA生物学的谜团。目的1:确定snoRNAome的细胞RNA靶点
通过一种先进的酮基化辅助RNA-RNA相互作用测序(KARR-seq)方法,
能够在转录组学规模上全面捕获和鉴定snoRNA-RNA相互作用。这些
结果将被用于确定snoRNA引导的mRNA序列靶向的规则。目标2将调查
两种类型的snoRNA-mRNA相互作用的转录组范围和调节基因的后果
通过应用新的测序方法来定位2 'O-甲基和假尿苷,
在前mRNA和成熟mRNA的修饰,并将这些结果与snoRNA-mRNA相互作用组。
我们还将选择性地删除snoRNA基因或敲低snoRNA水平,改变snoRNP的表达,
组分以研究特异性snoRNA-mRNA相互作用的结果。所有这些结果将
提供了第一个全面的snoRNA-RNA相互作用组,并推导出snoRNA-mRNA的指导原则
相互作用和相关的生物功能。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
CHUAN HE其他文献
CHUAN HE的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('CHUAN HE', 18)}}的其他基金
Targets and functions of the mammalian snoRNAome
哺乳动物 snoRNAome 的目标和功能
- 批准号:
10708950 - 财政年份:2022
- 资助金额:
$ 77.38万 - 项目类别:
Mechanosensitive M7G epitranscriptome in endothelial health and disease
机械敏感 M7G 表观转录组在内皮健康和疾病中的作用
- 批准号:
10367181 - 财政年份:2021
- 资助金额:
$ 77.38万 - 项目类别:
Mechanosensitive M7G epitranscriptome in endothelial health and disease
机械敏感 M7G 表观转录组在内皮健康和疾病中的作用
- 批准号:
10543139 - 财政年份:2021
- 资助金额:
$ 77.38万 - 项目类别:
Interrogation of dynamic RNA modifications in beta cells in type 1 diabetes
1 型糖尿病 β 细胞动态 RNA 修饰的研究
- 批准号:
9459617 - 财政年份:2017
- 资助金额:
$ 77.38万 - 项目类别:
Center for dynamic RNA epitranscriptomes - Renewal
动态 RNA 表观转录组中心 - 更新
- 批准号:
10434878 - 财政年份:2016
- 资助金额:
$ 77.38万 - 项目类别:
Center for dynamic RNA epitranscriptomes - Renewal
动态 RNA 表观转录组中心 - 更新
- 批准号:
10159493 - 财政年份:2016
- 资助金额:
$ 77.38万 - 项目类别:
Mapping the epigenome and transcriptome during hippocampal neurogenesis
绘制海马神经发生过程中的表观基因组和转录组图谱
- 批准号:
9975937 - 财政年份:2016
- 资助金额:
$ 77.38万 - 项目类别:
Center for dynamic RNA epitranscriptomes - Renewal
动态 RNA 表观转录组中心 - 更新
- 批准号:
10615783 - 财政年份:2016
- 资助金额:
$ 77.38万 - 项目类别:
Center for dynamic RNA epitranscriptomes - Covid 19 Supplement Version 2
动态 RNA 表观转录组中心 - Covid 19 补充版本 2
- 批准号:
10163382 - 财政年份:2016
- 资助金额:
$ 77.38万 - 项目类别:
相似海外基金
Development of Antisense Oligonucleotides to Regulate Gamma' Fibrinogen Levels
开发反义寡核苷酸来调节γ纤维蛋白原水平
- 批准号:
10759950 - 财政年份:2023
- 资助金额:
$ 77.38万 - 项目类别:
Inducing H3F3A exon skipping with antisense oligonucleotides as an approach to treat diffuse intrinsic pontine glioma
用反义寡核苷酸诱导 H3F3A 外显子跳跃作为治疗弥漫性内源性脑桥胶质瘤的方法
- 批准号:
10677284 - 财政年份:2023
- 资助金额:
$ 77.38万 - 项目类别:
Inducing PKM splice-switching with antisense oligonucleotides as an approach to treat hepatocellular carcinoma
用反义寡核苷酸诱导 PKM 剪接转换作为治疗肝细胞癌的方法
- 批准号:
10464020 - 财政年份:2022
- 资助金额:
$ 77.38万 - 项目类别:
Promoting adult hippocampal neurogenesis using antisense oligonucleotides as an Alzheimer's disease therapy
使用反义寡核苷酸促进成人海马神经发生作为阿尔茨海默氏病的治疗
- 批准号:
10484703 - 财政年份:2022
- 资助金额:
$ 77.38万 - 项目类别:
Strategy for specific delivery of antisense oligonucleotides to T cells
将反义寡核苷酸特异性递送至 T 细胞的策略
- 批准号:
10547347 - 财政年份:2022
- 资助金额:
$ 77.38万 - 项目类别:
Metabolism of Antisense Oligonucleotides and other Polyanions in Liver
反义寡核苷酸和其他聚阴离子在肝脏中的代谢
- 批准号:
10806783 - 财政年份:2022
- 资助金额:
$ 77.38万 - 项目类别:
Metabolism of Antisense Oligonucleotides and other Polyanions in Liver
反义寡核苷酸和其他聚阴离子在肝脏中的代谢
- 批准号:
10689248 - 财政年份:2022
- 资助金额:
$ 77.38万 - 项目类别:
Metabolism of Antisense Oligonucleotides and other Polyanions in Liver
反义寡核苷酸和其他聚阴离子在肝脏中的代谢
- 批准号:
10501862 - 财政年份:2022
- 资助金额:
$ 77.38万 - 项目类别:
Inducing PKM splice-switching with antisense oligonucleotides as an approach to treat hepatocellular carcinoma
用反义寡核苷酸诱导 PKM 剪接转换作为治疗肝细胞癌的方法
- 批准号:
10623180 - 财政年份:2022
- 资助金额:
$ 77.38万 - 项目类别:
Identifying binding partners, biological substrates and antisense oligonucleotides regulating expression of short and long ACE2.
识别调节短和长 ACE2 表达的结合伴侣、生物底物和反义寡核苷酸。
- 批准号:
BB/V019848/1 - 财政年份:2021
- 资助金额:
$ 77.38万 - 项目类别:
Research Grant