Role of m6A RNA modifications in AHR-mediated developmental toxicity

m6A RNA 修饰在 AHR 介导的发育毒性中的作用

基本信息

项目摘要

Project Summary The overall objective of this R21 proposal is to determine the extent to which environmental chemical exposures affect the most abundant epitranscriptomic mark, N6-methyl-adenosine (m6A) in developing vertebrate embryos. RNA, like DNA, undergo reversible chemical modifications that can potentially influence gene expression. Research so far indicates that m6A modification in mRNAs and ncRNAs plays a critical role in a number of physiological processes including embryonic development, metabolism, central nervous system function and circadian clock regulation. Altered m6A modification has also been linked to a number of disease states including cancer. As many environmental contaminants alter gene expression profiles and have detrimental effects on physiological processes, it is important to understand the effects of exposure on this important layer of gene regulation. Our preliminary results demonstrated that exposure to a dioxin-like polychlorinated biphenyl (PCB) and an aryl hydrocarbon receptor (AHR) during development alter m6A patterns in zebrafish. The proposed research has two specific aims. Aim 1 tests the hypothesis that a diverse group of AHR agonists will alter m6A RNA methylation patterns in a unique set of transcripts. Using three different environmentally relevant dioxin-like PCBs (AHR agonists), we will measure the dose-dependence and ligand-specificity of AHR's role in mediating developmental toxicity and altered m6A RNA methylation patterns. Zebrafish embryos will be exposed to toxicants to evaluate the m6A patterns using m6A individual-nucleotide-resolution cross-linking and immunoprecipitation (mi-CLIP). Using paired-end sequencing of RNA (RNAseq), we will determine the impact of altered m6A methylation on gene expression and mRNA splicing. In Aim 2, we will test the hypothesis that one or more of the players in m6A RNA methylation (m6A writer (mettl3), eraser (fto) and reader (ythdf2)) will have altered sensitivity to AHR agonists. We will expose zebrafish embryos from heterozgyous mutant crosses to different concentrations of an AHR agonist, and compare the sensitivity in responses between genotypes. The proposed research will establish the effects of diverse AHR ligands on m6A RNA methylation patterns, elucidate the impact of altered m6A methylation on gene expression and alternative (mRNA) splicing, and characterize the role of key RNA methylation proteins in toxicant- induced alteration of m6A patterns and gene regulation. These results will form the basis for future studies determining the potential roles of RNA methylation in developmental toxicity as well as developmental basis of adult health and disease.
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)

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 }}

NEELAKANTESWAR Aluru其他文献

NEELAKANTESWAR Aluru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('NEELAKANTESWAR Aluru', 18)}}的其他基金

Investigating the role of neuroinflammation in environmental exposure-induced anxiety disorders
研究神经炎症在环境暴露诱发的焦虑症中的作用
  • 批准号:
    10573948
  • 财政年份:
    2022
  • 资助金额:
    $ 45.48万
  • 项目类别:
Role of de novo DNMTs in Toxicant Induced Alterations in DNA Methylation
de novo DNMT 在毒物诱导的 DNA 甲基化改变中的作用
  • 批准号:
    8813984
  • 财政年份:
    2015
  • 资助金额:
    $ 45.48万
  • 项目类别:

相似海外基金

Impact of alternative polyadenylation of 3'-untranslated regions in the PI3K/AKT cascade on microRNA
PI3K/AKT 级联中 3-非翻译区的替代多聚腺苷酸化对 microRNA 的影响
  • 批准号:
    573541-2022
  • 财政年份:
    2022
  • 资助金额:
    $ 45.48万
  • 项目类别:
    University Undergraduate Student Research Awards
How do untranslated regions of cannabinoid receptor type 1 mRNA determine receptor subcellular localisation and function?
1 型大麻素受体 mRNA 的非翻译区如何决定受体亚细胞定位和功能?
  • 批准号:
    2744317
  • 财政年份:
    2022
  • 资助金额:
    $ 45.48万
  • 项目类别:
    Studentship
MICA:Synthetic untranslated regions for direct delivery of therapeutic mRNAs
MICA:用于直接递送治疗性 mRNA 的合成非翻译区
  • 批准号:
    MR/V010948/1
  • 财政年份:
    2021
  • 资助金额:
    $ 45.48万
  • 项目类别:
    Research Grant
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
  • 批准号:
    10019570
  • 财政年份:
    2019
  • 资助金额:
    $ 45.48万
  • 项目类别:
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
  • 批准号:
    10223370
  • 财政年份:
    2019
  • 资助金额:
    $ 45.48万
  • 项目类别:
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
  • 批准号:
    10455108
  • 财政年份:
    2019
  • 资助金额:
    $ 45.48万
  • 项目类别:
Synergistic microRNA-binding sites, and 3' untranslated regions: a dialogue of silence
协同的 microRNA 结合位点和 3 非翻译区:沉默的对话
  • 批准号:
    255762
  • 财政年份:
    2012
  • 资助金额:
    $ 45.48万
  • 项目类别:
    Operating Grants
Analysis of long untranslated regions in Nipah virus genome
尼帕病毒基因组长非翻译区分析
  • 批准号:
    20790351
  • 财政年份:
    2008
  • 资助金额:
    $ 45.48万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Search for mRNA elements involved in the compatibility between 5' untranslated regions and coding regions in chloroplast translation
寻找参与叶绿体翻译中 5 非翻译区和编码区之间兼容性的 mRNA 元件
  • 批准号:
    19370021
  • 财政年份:
    2007
  • 资助金额:
    $ 45.48万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Post-transcriptional Regulation of PPAR-g Expression by 5'-Untranslated Regions
5-非翻译区对 PPAR-g 表达的转录后调控
  • 批准号:
    7131841
  • 财政年份:
    2006
  • 资助金额:
    $ 45.48万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了