Regulation of Spermatogenesis by X-linked miRNAs
X 连锁 miRNA 对精子发生的调节
基本信息
- 批准号:8644815
- 负责人:
- 金额:$ 38.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-04-01 至 2016-03-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingActive SitesCell NucleusCell physiologyCellsCharacteristicsCollaborationsContraceptive AgentsCytoplasmDNADataDefectDevelopmentDiagnosisEmployee StrikesEuchromatinFemaleFertilityFunctional RNAGene ClusterGene SilencingGenesGermGerm CellsGrantIn VitroKnock-outLeadLinkMale InfertilityMediatingMeiosisMessenger RNAMicroRNAsMolecularMolecular GeneticsMolecular ProfilingMusNational Institute of Child Health and Human DevelopmentNuclearOrganPatternPhasePhysical condensationPlayPost-Transcriptional RegulationProcessProductionProphaseProteinsRegulationReportingRoleSex ChromosomesSomatic CellSpermatocytesSpermatogenesisSpermiogenesisStagingStructural GenesTechnologyTestingTestisTranslatingX ChromosomeX InactivationY Chromosomeblastomere structurechromatin modificationdeep sequencingdesigngene repressionhomologous recombinationin vivoinsightknockout genemRNA Stabilitymalemammalian genomemutantnovelpublic health relevancesexsperm cell
项目摘要
DESCRIPTION (provided by applicant): Meiotic sex chromosome inactivation (MSCI) during spermatogenesis is characterized by transcriptional silencing of genes on both the X and Y chromosomes in mid to late pachytene spermatocytes. MSCI is believed to result from meiotic silencing of unpaired DNA because the X and Y chromosomes remain largely unpaired throughout first meiotic prophase. Thus, unlike X-chromosome inactivation in female embryonic or somatic cells, where 25-30% of X-linked structural genes have been reported to escape inactivation, there have been no previous reports of genes that escape the silencing effects of MSCI in primary spermatocytes. However, we recently discovered that many X-linked microRNAs (miRNAs) are transcribed and processed in pachytene spermatocytes. This unprecedented escape from MSCI suggests that these miRNAs participate in one or more critical functions at this stage of spermatogenesis. This is corroborated by our preliminary finding that chimeric mice carrying a high percentage of cells bearing a knockout of a major cluster of X-linked miRNA genes display a fertility defect manifest as a block during the meiotic phase of spermatogenesis. This is significant because despite recent reports describing expression of an abundance of miRNAs and other small, non-coding RNAs during spermatogenesis, essentially nothing is known about the function of any of these. In this application, we first propose to investigate the molecular mechanism by which these X-linked miRNA genes escape MSCI (Aim 1). We then propose to test two hypotheses (which are not mutually exclusive) regarding function of these miRNAs, including their role as post- transcriptional regulators of autosomal mRNAs that are synthesized during meiosis but not translated until the postmeiotic period (Aim 2), and their role in regulating the process of MSCI itself (Aim 3). This study is highly novel in that it is designed to reveal an unprecedented mechanism of escape from MSCI, and to identify actual functions of those X-linked miRNAs that undergo this escape during spermatogenesis.
描述(由申请人提供):在精子发生过程中,减数分裂性染色体失活(MSCI)的特征是在粗线期中后期精子细胞中X染色体和Y染色体上的基因转录沉默。MSCI被认为是由于未配对DNA的减数分裂沉默,因为在第一次减数分裂前期,X和Y染色体在很大程度上保持未配对。因此,与女性胚胎或体细胞中的x染色体失活不同(据报道有25-30%的x连锁结构基因可以逃脱失活),在原代精母细胞中,没有关于基因可以逃脱MSCI沉默效应的报道。然而,我们最近发现许多X-linked microrna (mirna)在粗线精母细胞中被转录和加工。这种前所未有的MSCI逃逸表明,这些mirna在精子发生的这一阶段参与了一个或多个关键功能。我们的初步发现证实了这一点,即嵌合小鼠携带高百分比的细胞,携带一个主要的x连锁miRNA基因簇的敲除,在精子发生的减数分裂阶段表现为生育缺陷。这一点很重要,因为尽管最近的报道描述了在精子发生过程中大量的mirna和其他小的非编码rna的表达,但基本上对这些rna的功能一无所知。在本应用中,我们首先提出研究这些x连锁miRNA基因逃避MSCI的分子机制(Aim 1)。然后,我们提议测试关于这些mirna功能的两种假设(这两种假设并不相互排斥),包括它们作为常染色体mrna的转录后调节剂的作用,这些mrna在减数分裂期间合成,但直到减数分裂后才翻译(Aim 2),以及它们在调节MSCI本身过程中的作用(Aim 3)。这项研究非常新颖,因为它旨在揭示一种前所未有的逃避MSCI的机制,并确定在精子发生过程中经历这种逃避的X-linked mirna的实际功能。
项目成果
期刊论文数量(20)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mark it for destruction: a novel role of mRNA methylation in maternal-to-zygotic transition†.
将其标记为破坏:mRNA 甲基化在母体向合子转变中的新作用。
- DOI:10.1093/biolre/iox016
- 发表时间:2017
- 期刊:
- 影响因子:3.6
- 作者:Yan,Wei
- 通讯作者:Yan,Wei
Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation.
- DOI:10.1038/nature11171
- 发表时间:2012-07-12
- 期刊:
- 影响因子:64.8
- 作者:Grant, Jennifer;Mahadevaiah, Shantha K.;Khil, Pavel;Sangrithi, Mahesh N.;Royo, Helene;Duckworth, Janine;McCarrey, John R.;VandeBerg, John L.;Renfree, Marilyn B.;Taylor, Willie;Elgar, Greg;Camerini-Otero, R. Daniel;Gilchrist, Mike J.;Turner, James M. A.
- 通讯作者:Turner, James M. A.
SpermBase: A Database for Sperm-Borne RNA Contents.
- DOI:10.1095/biolreprod.116.142190
- 发表时间:2016-11-01
- 期刊:
- 影响因子:3.6
- 作者:Schuster A;Tang C;Xie Y;Ortogero N;Yuan S;Yan W
- 通讯作者:Yan W
piRNA-independent PIWI function in spermatogenesis and male fertility.
不依赖于 piRNA 的 PIWI 在精子发生和男性生育能力中发挥作用。
- DOI:10.1093/biolre/iox055
- 发表时间:2017
- 期刊:
- 影响因子:3.6
- 作者:YanEditor-In-ChiefBiologyOfReproduction,Wei
- 通讯作者:YanEditor-In-ChiefBiologyOfReproduction,Wei
UPF2-Dependent Nonsense-Mediated mRNA Decay Pathway Is Essential for Spermatogenesis by Selectively Eliminating Longer 3'UTR Transcripts.
- DOI:10.1371/journal.pgen.1005863
- 发表时间:2016-05
- 期刊:
- 影响因子:4.5
- 作者:Bao J;Vitting-Seerup K;Waage J;Tang C;Ge Y;Porse BT;Yan W
- 通讯作者:Yan W
{{
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 }}
John R MCCARREY其他文献
John R MCCARREY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('John R MCCARREY', 18)}}的其他基金
Germline-mediated Transgenerational Epigenetic Inheritance of Paternal Epimutations Induced by a High Fat Diet
高脂肪饮食诱导的种系介导的父本表观突变的跨代表观遗传
- 批准号:
10615593 - 财政年份:2019
- 资助金额:
$ 38.4万 - 项目类别:
Germline-mediated Transgenerational Epigenetic Inheritance of Paternal Epimutations Induced by a High Fat Diet
高脂肪饮食诱导的种系介导的父本表观突变的跨代表观遗传
- 批准号:
10260436 - 财政年份:2019
- 资助金额:
$ 38.4万 - 项目类别:
Germline-mediated Transgenerational Epigenetic Inheritance of Paternal Epimutations Induced by a High Fat Diet
高脂肪饮食诱导的种系介导的父本表观突变的跨代表观遗传
- 批准号:
10018080 - 财政年份:2019
- 资助金额:
$ 38.4万 - 项目类别:
Epimutations in Offspring Produced by Assisted Reproductive Technologies (ART)
辅助生殖技术 (ART) 产生的后代的表观突变
- 批准号:
8757199 - 财政年份:2014
- 资助金额:
$ 38.4万 - 项目类别:
2014 Mammalian Reproduction Gordon Research Conference
2014年哺乳动物繁殖戈登研究会议
- 批准号:
8776096 - 财政年份:2014
- 资助金额:
$ 38.4万 - 项目类别:
Regulation of Spermatogenesis by X-linked miRNAs
X 连锁 miRNA 对精子发生的调节
- 批准号:
8050092 - 财政年份:2010
- 资助金额:
$ 38.4万 - 项目类别:
Regulation of Spermatogenesis by X-linked miRNAs
X 连锁 miRNA 对精子发生的调节
- 批准号:
8447585 - 财政年份:2010
- 资助金额:
$ 38.4万 - 项目类别:
Regulation of Spermatogenesis by X-linked miRNAs
X 连锁 miRNA 对精子发生的调节
- 批准号:
7889745 - 财政年份:2010
- 资助金额:
$ 38.4万 - 项目类别:
Regulation of Spermatogenesis by X-linked miRNAs
X 连锁 miRNA 对精子发生的调节
- 批准号:
8241155 - 财政年份:2010
- 资助金额:
$ 38.4万 - 项目类别:
相似海外基金
Collaborative Research: Beyond the Single-Atom Paradigm: A Priori Design of Dual-Atom Alloy Active Sites for Efficient and Selective Chemical Conversions
合作研究:超越单原子范式:双原子合金活性位点的先验设计,用于高效和选择性化学转化
- 批准号:
2334970 - 财政年份:2024
- 资助金额:
$ 38.4万 - 项目类别:
Standard Grant
NSF-BSF: Towards a Molecular Understanding of Dynamic Active Sites in Advanced Alkaline Water Oxidation Catalysts
NSF-BSF:高级碱性水氧化催化剂动态活性位点的分子理解
- 批准号:
2400195 - 财政年份:2024
- 资助金额:
$ 38.4万 - 项目类别:
Standard Grant
Collaborative Research: Beyond the Single-Atom Paradigm: A Priori Design of Dual-Atom Alloy Active Sites for Efficient and Selective Chemical Conversions
合作研究:超越单原子范式:双原子合金活性位点的先验设计,用于高效和选择性化学转化
- 批准号:
2334969 - 财政年份:2024
- 资助金额:
$ 38.4万 - 项目类别:
Standard Grant
Mechanochemical synthesis of nanocarbon and design of active sites for oxygen reducton/evolution reactions
纳米碳的机械化学合成和氧还原/演化反应活性位点的设计
- 批准号:
23K04919 - 财政年份:2023
- 资助金额:
$ 38.4万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Creation of porous inorganic frameworks with controlled structure of metal active sites by the building block method.
通过积木法创建具有金属活性位点受控结构的多孔无机框架。
- 批准号:
22KJ2957 - 财政年份:2023
- 资助金额:
$ 38.4万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Catalysis of Juxaposed Active Sites Created in Nanospaces and Their Applications
纳米空间中并置活性位点的催化及其应用
- 批准号:
23K04494 - 财政年份:2023
- 资助金额:
$ 38.4万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Generation of carbon active sites by modifying the oxygen containing functional groups and structures of carbons for utilizing to various catalytic reactions.
通过修饰碳的含氧官能团和结构来产生碳活性位点,用于各种催化反应。
- 批准号:
23K13831 - 财政年份:2023
- 资助金额:
$ 38.4万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
CAREER: CAS: Understanding the Chemistry of Palladium and Silyl Compounds to Design Catalyst Active Sites
职业:CAS:了解钯和甲硅烷基化合物的化学性质以设计催化剂活性位点
- 批准号:
2238379 - 财政年份:2023
- 资助金额:
$ 38.4万 - 项目类别:
Continuing Grant
CAS: Collaborative Research: Tailoring the Distribution of Transient vs. Dynamic Active Sites in Solid-Acid Catalysts and Their Impacts on Chemical Conversions
CAS:合作研究:定制固体酸催化剂中瞬时活性位点与动态活性位点的分布及其对化学转化的影响
- 批准号:
2154399 - 财政年份:2022
- 资助金额:
$ 38.4万 - 项目类别:
Standard Grant
Engineering of Active Sites in Heterogeneous Catalysts for Sustainable Chemical and Fuel Production.
用于可持续化学和燃料生产的多相催化剂活性位点工程。
- 批准号:
RGPIN-2019-06633 - 财政年份:2022
- 资助金额:
$ 38.4万 - 项目类别:
Discovery Grants Program - Individual