Small RNA-mediated Translation Repression in Chlamydomonas
衣藻中小 RNA 介导的翻译抑制
基本信息
- 批准号:1244576
- 负责人:
- 金额:$ 56.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-05-01 至 2018-04-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Intellectual Merit: The growth and development of eukaryotes is determined by complex interactions between their genetic make-up and the environment. In multicellular organisms, the different types of cells, tissues, and organs are ultimately defined by differential gene expression. Small RNAs (~20-30 nucleotides in length) play important roles in gene regulation as well as in defense responses against parasitic genomic elements such as transposons and viruses. The biogenesis and mode of action of these noncoding RNAs have attracted great attention in recent years, but many aspects of small RNA (sRNA) function are still poorly characterized. One central problem is our incomplete understanding of the factors involved in these processes. Interestingly, in the green alga Chlamydomonas reinhardtii, sRNAs perfectly complementary to a target transcript can inhibit protein synthesis without or with only minimal mRNA destabilization. This mechanism operates at a post-initiation step of translation and appears to alter the function/structural conformation of translating ribosomes so that they display reduced sensitivity to inhibition by some antibiotics such as cycloheximide. Evidence for sRNA-repressed transcripts remaining associated with polyribosomes, a strong argument in support of post-initiation translation inhibition, also exists in several other eukaryotes. The project will focus on the mechanistic characterization of this relatively unexplored process. It will involve the identification of molecular components of sRNA-guided effector complexes, involved in post-initiation translation repression, and the isolation and analysis of algal mutants defective in this process. The research will also characterize endogenous transcripts preferentially repressed by sRNAs at the translational level and begin addressing the role(s) of small RNAs in algal biology. Chlamydomonas offers an advantage for the isolation and characterization of novel factors involved in sRNA-mediated translation repression since the RNA interference (RNAi) machinery, despite being fairly complex, is not required for organismal viability. Moreover, novel mechanistic insights may be obtained through these studies because algae and land plants appear to lack orthologs of several of the proteins implicated in sRNA-mediated post-transcriptional regulation in metazoans. Characterization of RNAi in evolutionarily divergent eukaryotes is expected to contribute to our understanding of both common as well as lineage-specific mechanisms of sRNA-mediated silencing.Broader ImpactsThe project will have an impact on human resource development through the direct training of undergraduate and graduate students and one postdoctoral fellow. Students will learn research methodology via hands on experience, with the goal of fostering their interest in scientific discovery. The laboratory findings will be used to stimulate the learning process and to promote discussions on the benefits of algal/plant science research in two plant biology courses. The training of a postdoctoral fellow for a career which combines research and education is also a central component of the project. Additionally, students will participate in a number of programs devoted to the instruction of minority individuals and in outreach activities with a non-profit organization working to educate the public on the nature and importance of science. The results of the project may also have practical implications for the genetic improvement of algal strains for biofuel production. One key constraint for the commercial development of algal feedstocks is the very limited knowledge on the regulatory mechanisms that control gene expression and metabolism. The anticipated findings will contribute useful information for understanding the function of small RNAs in microalgae and for the development of tools to modulate gene expression.
智力优点:真核生物的生长和发育是由其遗传组成与环境之间复杂的相互作用决定的。在多细胞生物体中,不同类型的细胞、组织和器官最终由差异基因表达来定义。小RNA(长度约20-30个核苷酸)在基因调控以及针对转座子和病毒等寄生基因组元件的防御反应中发挥着重要作用。近年来,这些非编码RNA的生物发生和作用模式引起了人们的极大关注,但小RNA(sRNA)功能的许多方面仍然知之甚少。一个核心问题是我们对这些过程中涉及的因素的不完全理解。有趣的是,在绿藻莱茵衣藻中,与目标转录物完美互补的 sRNA 可以抑制蛋白质合成,而不会或只有极小的 mRNA 不稳定。该机制在翻译起始后步骤中起作用,并且似乎改变了翻译核糖体的功能/结构构象,使得它们对某些抗生素(例如放线菌酮)的抑制表现出降低的敏感性。 sRNA 抑制转录物仍然与多核糖体相关的证据,是支持起始后翻译抑制的有力论据,也存在于其他几种真核生物中。该项目将重点关注这一相对未经探索的过程的机械特征。它将涉及 sRNA 引导效应复合物分子成分的鉴定,参与启动后翻译抑制,以及分离和分析该过程中有缺陷的藻类突变体。该研究还将表征在翻译水平上被 sRNA 优先抑制的内源转录本,并开始解决小 RNA 在藻类生物学中的作用。衣藻为分离和表征参与 sRNA 介导的翻译抑制的新因子提供了优势,因为 RNA 干扰 (RNAi) 机制尽管相当复杂,但并不是生物体生存所必需的。此外,通过这些研究可以获得新的机制见解,因为藻类和陆地植物似乎缺乏与后生动物中 sRNA 介导的转录后调节有关的几种蛋白质的直系同源物。进化上不同的真核生物中 RNAi 的表征预计将有助于我们了解 sRNA 介导的沉默的常见机制和谱系特异性机制。 更广泛的影响该项目将通过对本科生和研究生的直接培训对人力资源开发产生影响和一名博士后。学生将通过实践经验学习研究方法,目的是培养他们对科学发现的兴趣。实验室研究结果将用于刺激学习过程,并促进两门植物生物学课程中关于藻类/植物科学研究的好处的讨论。对博士后研究员进行研究和教育相结合的职业培训也是该项目的核心组成部分。此外,学生还将参加一些专门针对少数群体的指导项目,以及与非营利组织合作的外展活动,该组织致力于教育公众科学的本质和重要性。该项目的结果也可能对用于生物燃料生产的藻类菌株的遗传改良具有实际意义。藻类原料商业开发的一个关键限制是对控制基因表达和代谢的调控机制的了解非常有限。预期的发现将为理解微藻中小RNA的功能和开发调节基因表达的工具提供有用的信息。
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 }}
Heriberto Cerutti其他文献
クラミドモナスmiRNAを介した遺伝子発現抑制はseed配列の相同性のみで誘導される
衣藻 miRNA 介导的基因表达抑制仅由种子序列同源性诱导
- DOI:
- 发表时间:
2013 - 期刊:
- 影响因子:0
- 作者:
山崎朋人;Heriberto Cerutti;大濱武 - 通讯作者:
大濱武
MLK4-mediated phosphorylation of histone H3T3 promoters flowering by transcriptional silencing of FLC/MAF in Arabidopsis thaliana
拟南芥中 MLK4 介导的组蛋白 H3T3 启动子磷酸化通过转录沉默 FLC/MAF 开花
- DOI:
- 发表时间:
2020 - 期刊:
- 影响因子:0
- 作者:
Zhen Wang;Junmei Kang;Juan Arm;o Casas-Mollano;Yongchao Dou;Shangang Jia;Qingchuan Yang;Chi Zhang;Heriberto Cerutti - 通讯作者:
Heriberto Cerutti
単細胞緑藻クラミドモナスを用いたRNAサイレンシング機構の解析
利用单细胞绿藻衣藻分析 RNA 沉默机制
- DOI:
- 发表时间:
2013 - 期刊:
- 影响因子:0
- 作者:
山崎朋人;Heriberto Cerutti;大濱武 - 通讯作者:
大濱武
クラミドモナスmiRNAを介した遺伝子発現抑制はseed配列の相同性のみで誘導される
衣藻 miRNA 介导的基因表达抑制仅由种子序列同源性诱导
- DOI:
- 发表时间:
2013 - 期刊:
- 影响因子:0
- 作者:
山崎朋人;Heriberto Cerutti;大濱武 - 通讯作者:
大濱武
単細胞緑藻クラミドモナスを用いたRNAサイレンシング機構の解析
利用单细胞绿藻衣藻分析 RNA 沉默机制
- DOI:
- 发表时间:
2013 - 期刊:
- 影响因子:0
- 作者:
山崎朋人;Heriberto Cerutti;大濱武 - 通讯作者:
大濱武
Heriberto Cerutti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('Heriberto Cerutti', 18)}}的其他基金
Mechanisms of Small RNA-Mediated Silencing in Chlamydomonas
衣藻中小 RNA 介导的沉默机制
- 批准号:
2131783 - 财政年份:2022
- 资助金额:
$ 56.69万 - 项目类别:
Standard Grant
REU Site: Integrated Development of Bioenergy Systems
REU网站:生物能源系统综合开发
- 批准号:
2050574 - 财政年份:2021
- 资助金额:
$ 56.69万 - 项目类别:
Standard Grant
Mechanisms of small RNA-mediated translation repression in Chlamydomonas
衣藻中小 RNA 介导的翻译抑制机制
- 批准号:
1616863 - 财政年份:2016
- 资助金额:
$ 56.69万 - 项目类别:
Standard Grant
Histone H3 Phosphorylation and Gene Silencing in Chlamydomonas and Arabidopsis
衣藻和拟南芥中的组蛋白 H3 磷酸化和基因沉默
- 批准号:
1052281 - 财政年份:2011
- 资助金额:
$ 56.69万 - 项目类别:
Continuing Grant
Histone Modifications and Transcriptional Silencing in Chlamydomonas
衣藻中的组蛋白修饰和转录沉默
- 批准号:
0544448 - 财政年份:2006
- 资助金额:
$ 56.69万 - 项目类别:
Continuing Grant
Transcriptional Gene Silencing in Chlamydomonas and Arabidopsis
衣藻和拟南芥中的转录基因沉默
- 批准号:
0131357 - 财政年份:2002
- 资助金额:
$ 56.69万 - 项目类别:
Continuing Grant
Epigenetic Silencing of Nuclear Transgenes in Chlamydomonas
衣藻核转基因的表观遗传沉默
- 批准号:
9808473 - 财政年份:1998
- 资助金额:
$ 56.69万 - 项目类别:
Standard Grant
相似国自然基金
长非编码RNA-MOS介导SMAD3蛋白O-GlcNAc糖基化修饰促进非小细胞肺癌转移的机制研究
- 批准号:82373007
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
拷贝数扩增驱动的长链非编码RNA ZFAND2A-DT 通过介导“相分离”调控线粒体谷氨酰胺代谢促进非小细胞肺癌发生发展机制研究
- 批准号:
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
甜菜严重曲顶病毒次级小RNA介导的植物抗病毒机制
- 批准号:
- 批准年份:2022
- 资助金额:30 万元
- 项目类别:青年科学基金项目
LANCL2-FLNA-hnRNPA1复合物介导的RNA剪接调控非小细胞肺癌EGFR-TKI耐药的机制研究
- 批准号:
- 批准年份:2022
- 资助金额:51 万元
- 项目类别:面上项目
小RNA介导的组蛋白修饰参与调控真菌致病性的分子机制
- 批准号:
- 批准年份:2022
- 资助金额:54 万元
- 项目类别:面上项目
相似海外基金
Silica Nanocapsule-Mediated Nonviral Delivery of CRISPR Base Editor mRNA and Allele Specific sgRNA for Gene Correction in Leber Congenital Amaurosis
二氧化硅纳米胶囊介导的 CRISPR 碱基编辑器 mRNA 和等位基因特异性 sgRNA 非病毒传递用于 Leber 先天性黑蒙的基因校正
- 批准号:
10668166 - 财政年份:2023
- 资助金额:
$ 56.69万 - 项目类别:
Gene Modulation of Acetylation Modifiers to Reveal Regulatory Links to Human Cardiac Electromechanics
乙酰化修饰剂的基因调节揭示与人类心脏机电的调节联系
- 批准号:
10677295 - 财政年份:2023
- 资助金额:
$ 56.69万 - 项目类别:
Targeting epigenetic machinery to overcome myeloid cell-mediated resistance to anti-PD-1 therapy in GBM
靶向表观遗传机制克服 GBM 中骨髓细胞介导的抗 PD-1 治疗耐药性
- 批准号:
10634277 - 财政年份:2023
- 资助金额:
$ 56.69万 - 项目类别:
Targeting the microtubule cytoskeleton to promote cavernous nerve regeneration and erectile function after injury
靶向微管细胞骨架促进损伤后海绵体神经再生和勃起功能
- 批准号:
10719124 - 财政年份:2023
- 资助金额:
$ 56.69万 - 项目类别:
Cellular perturbations to enhance precise therapeutic genome editing to treat FTD/ALS
细胞扰动增强精确治疗基因组编辑以治疗 FTD/ALS
- 批准号:
10607752 - 财政年份:2023
- 资助金额:
$ 56.69万 - 项目类别: