ERK-mediated regulation of non-coding RNAs during development and disease
发育和疾病过程中 ERK 介导的非编码 RNA 调节
基本信息
- 批准号:10673715
- 负责人:
- 金额:$ 40.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-10 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:AreaArginineBiogenesisBiological AssayBiologyBirthCRISPR/Cas technologyCaenorhabditis elegansCell Culture SystemCellsCongenital AbnormalityDevelopmentDiseaseEmbryoEmbryonic DevelopmentEndometrial CarcinomaEventGenerationsGrowth FactorHumanHuman BiologyImageInfertilityInvestigationKnowledgeLightLinkMalignant NeoplasmsMammalian CellMammalsMediatingMeiosisMethodsMethylationModelingMorphogenesisOocytesPhosphorylationPopulationProcessProteomeProteomicsPubertyRNARNA DegradationRegulationReproductionResearchRoleSignal TransductionSmall RNASterilityUntranslated RNAWorkexosomegenome editinghuman femalein vivo Modelmouse modelnext generation sequencingoocyte qualitysperm celltranscriptome
项目摘要
PROJECT SUMMARY
Successful reproduction through the fusion of the sperm and oocyte is essential for the perpetuation of species.
In human females, oocytes complete meiosis I at birth, and enter a long period of meiotic II arrest until
onset of meiotic maturation at puberty. Because the oocytes are quiescent and arrested during this period,
RNAs are loaded into the developing oocytes prior to the arrest and these RNAs are critical for early
embryonic development. Mechanisms that regulate generation and protection (from degradation) of
maternal RNAs during the long meiotic arrest as well as mechanisms that regulate the degradation of these
RNAs in the embryo remain an active area of investigation. Our work in C. elegans and work from mammalian
models in the past few years turned the light on regulation of the maternal transcriptome which dictates oocyte
quality and impacts progeny development. Specifically, we uncovered a direct link between RAS/ERK growth
factor signaling and the small RNA biogenesis factors Dicer1, Drosha and DIS3 (an RNA exosomal component)
which regulates distinct populations of small non-coding RNAs and thus the maternal transcriptome and
proteome. We propose a model wherein ERK-mediated phosphorylation of Dicer1 (and a subsequent arginine
methylation of Dicer1), phosphorylation of Drosha and DIS3 results in a regulatory circuit that fine tunes the
generation of small non-coding RNAs in specific subsets and regulates the maternal and zygotic transcriptome
and proteome. We investigate this model in vivo during oocyte development and oocyte-to-embryo transition
using a combination of live imaging, next generation sequencing, single oocyte sequencing, mass spectrometric
and proteomic methods, CRISPR Cas9 genome editing and cell biological assays. We find that Dicer1, Drosha
and Dis3 are phosphorylated in mammals as well. Additionally, we identified arginine methylation of Dicer1
adjacent to the phosphorylation event in mammalian cell culture system. Given their conserved role in RNA
biology, reproduction and their aberrations associated with cancer onset and progression, we expect this work
to have direct relevance to human biology.
项目摘要
通过精子和卵母细胞的融合成功繁殖对于物种的延续是必不可少的。
在人类女性中,卵母细胞在出生时完成减数分裂I,并进入长时间的减数分裂II停滞期,直到
在青春期开始减数分裂成熟。因为卵母细胞在此期间处于静止和停滞状态,
RNA在停滞前被加载到发育中的卵母细胞中,这些RNA对于早期发育至关重要。
胚胎发育调节生物质的产生和保护(免于退化)的机制
母体RNA在长减数分裂停滞期间以及调节这些降解的机制,
胚胎中的RNA仍然是一个活跃的研究领域。我们在C的工作哺乳动物的研究
在过去几年中,一些模型揭示了决定卵母细胞的母体转录组的调控
质量和影响后代发育。具体来说,我们发现RAS/ERK的增长与
因子信号传导和小RNA生物合成因子Dicer 1、Drosha和DIS 3(RNA外泌体组分)
其调节小的非编码RNA的不同群体,从而调节母体转录组,
蛋白质组我们提出了一个模型,其中ERK介导的Dicer 1磷酸化(和随后的精氨酸
Dicer 1的甲基化)、Drosha和DIS 3的磷酸化导致了一个调节回路,
在特定亚群中产生小的非编码RNA,并调节母体和合子转录组
和蛋白质组。我们在卵母细胞发育和卵母细胞向胚胎转化过程中研究了这种模型
使用实时成像、下一代测序、单个卵母细胞测序、质谱
和蛋白质组学方法、CRISPR Cas9基因组编辑和细胞生物学测定。我们发现Dicer 1,Drosha
和Dis 3在哺乳动物中也被磷酸化。此外,我们鉴定了Dicer 1的精氨酸甲基化,
与哺乳动物细胞培养系统中的磷酸化事件相邻。鉴于它们在RNA中的保守作用
生物学,生殖及其与癌症发病和进展相关的畸变,我们期待这项工作
与人类生物学直接相关。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
sart-3 functions to regulate germline sex determination in C. elegans .
SART-3功能可调节秀丽隐杆线虫中种系性别的确定。
- DOI:10.17912/micropub.biology.000820
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Furuta, Tokiko;Arur, Swathi
- 通讯作者:Arur, Swathi
{{
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 }}
Swathi Arur其他文献
Swathi Arur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('Swathi Arur', 18)}}的其他基金
Spatio-temporal regulation of ERK signaling by phosphatases in the female germline
雌性种系中磷酸酶对 ERK 信号传导的时空调节
- 批准号:
10571433 - 财政年份:2023
- 资助金额:
$ 40.5万 - 项目类别:
2023 Developmental Biology Gordon Research Conference and Gordon Research Seminar
2023年发育生物学戈登研究会议暨戈登研究研讨会
- 批准号:
10683608 - 财政年份:2023
- 资助金额:
$ 40.5万 - 项目类别:
ERK-mediated regulation of non-coding RNAs during development and disease
发育和疾病过程中 ERK 介导的非编码 RNA 调节
- 批准号:
10487399 - 财政年份:2021
- 资助金额:
$ 40.5万 - 项目类别:
ERK mediated regulation of RbAp46/48 during female germ cell development
ERK 介导的雌性生殖细胞发育过程中 RbAp46/48 的调节
- 批准号:
10612853 - 财政年份:2020
- 资助金额:
$ 40.5万 - 项目类别:
ERK mediated regulation of RbAp46/48 during female germ cell development
ERK 介导的雌性生殖细胞发育过程中 RbAp46/48 的调节
- 批准号:
10388221 - 财政年份:2020
- 资助金额:
$ 40.5万 - 项目类别:
ERK mediated regulation of RbAp46/48 during female germ cell development
ERK 介导的雌性生殖细胞发育过程中 RbAp46/48 的调节
- 批准号:
10219320 - 财政年份:2020
- 资助金额:
$ 40.5万 - 项目类别:
Erk-mediated regulation of Dicer and Drosha function in C. elegans
Erk 介导的线虫 Dicer 和 Drosha 功能调节
- 批准号:
8729492 - 财政年份:2011
- 资助金额:
$ 40.5万 - 项目类别:
Erk-mediated regulation of Dicer and Drosha function in C. elegans
Erk 介导的线虫 Dicer 和 Drosha 功能调节
- 批准号:
8147376 - 财政年份:2011
- 资助金额:
$ 40.5万 - 项目类别:
Erk-mediated regulation of Dicer and Drosha function in C. elegans
Erk 介导的线虫 Dicer 和 Drosha 功能调节
- 批准号:
8323245 - 财政年份:2011
- 资助金额:
$ 40.5万 - 项目类别:
Erk-mediated regulation of Dicer and Drosha function in C. elegans
Erk 介导的线虫 Dicer 和 Drosha 功能调节
- 批准号:
8535274 - 财政年份:2011
- 资助金额:
$ 40.5万 - 项目类别:
相似国自然基金
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
- 批准号:81973577
- 批准年份:2019
- 资助金额:55.0 万元
- 项目类别:面上项目
相似海外基金
Targeting protein arginine methylation in the 9p21.3 loss tumor microenvironment
9p21.3 缺失肿瘤微环境中的靶向蛋白精氨酸甲基化
- 批准号:
489995 - 财政年份:2023
- 资助金额:
$ 40.5万 - 项目类别:
Operating Grants
The role of protein arginine methyl transferase PRMT1 on myelin development
蛋白精氨酸甲基转移酶PRMT1对髓磷脂发育的作用
- 批准号:
23K14287 - 财政年份:2023
- 资助金额:
$ 40.5万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Normalizing arginine metabolism with sepiaptein for immunostimulatory-shift ofHER2+ breast cancer
使用 Sepiaptein 使精氨酸代谢正常化以实现 HER2 乳腺癌的免疫刺激转变
- 批准号:
10776256 - 财政年份:2023
- 资助金额:
$ 40.5万 - 项目类别:
Effects of Arginine Depletion Combined with Platinum-Taxane Chemotherapy in Aggressive Variant Prostate Cancers (AVPC)
精氨酸消耗联合铂类紫杉烷化疗对侵袭性变异前列腺癌 (AVPC) 的影响
- 批准号:
10715329 - 财政年份:2023
- 资助金额:
$ 40.5万 - 项目类别:
Understanding resistance mechanisms to protein arginine methyltransransferase Inhibitors in Lymphoma
了解淋巴瘤对蛋白精氨酸甲基转移酶抑制剂的耐药机制
- 批准号:
10668754 - 财政年份:2023
- 资助金额:
$ 40.5万 - 项目类别:
Physiological function of arginine signaling:macropinocytosisand tumor immune evasion
精氨酸信号的生理功能:巨胞饮作用与肿瘤免疫逃避
- 批准号:
23H03317 - 财政年份:2023
- 资助金额:
$ 40.5万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Targeting protein arginine methylation in the 9p21.3 loss tumor microenvironment
9p21.3 缺失肿瘤微环境中的靶向蛋白精氨酸甲基化
- 批准号:
498862 - 财政年份:2023
- 资助金额:
$ 40.5万 - 项目类别:
Operating Grants
Regulation of androgen receptor signaling in prostate cancer by protein arginine methylation
通过蛋白质精氨酸甲基化调节前列腺癌中的雄激素受体信号传导
- 批准号:
10584689 - 财政年份:2023
- 资助金额:
$ 40.5万 - 项目类别:
Arginine methylation of the RNA helicase DDX5 in the regulation of RNA/DNA hybrids during the DNA damage response.
RNA 解旋酶 DDX5 的精氨酸甲基化在 DNA 损伤反应期间调节 RNA/DNA 杂交体中的作用。
- 批准号:
487619 - 财政年份:2023
- 资助金额:
$ 40.5万 - 项目类别:
Operating Grants
Regulation of and Target Recognition by Protein Arginine Methyltransferase 1 (PRMT1)
蛋白质精氨酸甲基转移酶 1 (PRMT1) 的调节和目标识别
- 批准号:
10653465 - 财政年份:2023
- 资助金额:
$ 40.5万 - 项目类别:














{{item.name}}会员




