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.
项目总结
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
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Swathi Arur的其他文献
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{{ 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:
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