REGULATED MRNA TRANSLATION IN DROSOPHILA BODY PATTERNING

果蝇身体模式中的 mRNA 翻译调控

基本信息

  • 批准号:
    2392288
  • 负责人:
  • 金额:
    $ 19.27万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1995
  • 资助国家:
    美国
  • 起止时间:
    1995-09-30 至 2000-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION: Dr. Paul Macdonald proposes a study of translational control in Drosophila development. Specifically, he is interested in the mechanisms by which translational regulation occurs and the roles that this level of control plays in embryonic patterning. Mechanisms for maintaining maternal messages in a translationally silent state have long been studied, mostly in developmental systems not amenable to genetic analysis. In most cases, these studies are directed at general mechanisms. Evidence has mounted, primarily in C. elegans and Drosophila for translational control of specific mRNAs as an aspect of regulation of patterning and other critical developmental mechanisms. Dr. Macdonald has been investigating the patterning gene oskar (osk) and has learned that osk function depends both on transcript localization and on translational regulation. osk functions in the targeting of posterior axis and germ cell determinants to the posterior end of the embryo. osk mRNA is itself localized posteriorly, and its activity is confined to that region. Mutations in osk lead to the mislocalization of the posterior axis determinant, nanos. In previous work on this system, the Macdonald lab learned that there is an interval between osk mRNA synthesis and its movement to a posterior position. During this interval, osk protein is not expressed. The protein only becomes detectable after localization of the message has occurred. The most reasonable explanation for this observation is that translation is repressed, probably via bound proteins. In spite of extensive studies of posterior group genes, none had surfaced that are likely candidates for this type of repressor function. Therefore, a biochemical search was conducted using a uv cross-linking assay. An 80 kD protein was identified, obp80, which binds specifically to three regions in the 3' UTR of osk mRNA. The three binding regions are related in sequence. Small changes in this sequence destroyed binding capacity. The level of obp 80 was found to be normal in all other posterior group mutants tested, confirming that no likely candidates for this function were known. Transgenes lacking the binding elements express RNAs that are localized normally, but which are translated prematurely, thereby separating these two elements of patterning gene expression. This proposal initially proposed alternate strategies for obtaining the obp 80 gene and pure protein. However, since submission of the proposal the gene was isolated via screens of expression libraries and sequenced and antibodies have been made. The protein obtained is consistent with predicted size, has the expected binding properties and contains three RNP binding domains, each different in sequence. The distinct binding domains result in a prediction that each is likely to have distinct binding preferences and further that osk is likely to be only one of several RNA targets. The specific aims of this portion of the grant are therefore revised in part. The aims are to correlate the binding of the obp 80 protein, now renamed bruno and with changes in poly A tail lenth, cap dependence. Plans are described for exploring further the parameters of binding, with emphasis now changed to address the capacities of the three different bruno binding domains. in vitro systems are described to explore the mechanism of translational repression in the absence of complicating developmental processes. in vitro translation systems and cell cutures will be tested for their suitability for manipulating bruno regulation of translation. Genetic analysi of bruno has been given high priority. A cytological locaton will be determined, follwed by a search of deficiencies and known mutations in the region. If such mutations are not found, full scale mutagenesis is planned. The second part of this proposal concerns the gene aubergine. The Macdonald lab isolated two new alleles of this previously discovered gene in a screen for the suppression of a bicaudal phenotype caused by mislocalization of osk RNA to the anterior end. Characterization of the phenotypes of these mutants revealed patterning defects along the dorsal-ventral axis. Working on the hypothesis that the gene functions in anterior-posterior and dorsovetral patterning, the effects of aub mutations on genes involved in one or the other patterning pathway were studied. Most localized messages were unaffected. However, osk and gerken proteins are absent and bcd is reduced in aub mutants. Aub therefore appears to be necessary for protein expression. An osk trangene with a bcd 3' UTR produces osk protein equally in wildtype and aub mutant backgrounds, showing that aub does not act by affecting protein stability, but that it does require 3' sequence elements. Experiments planned for aub are directed towards a more detailed description of aub action. Elements of osk and grk RNA required for aub function will be mapped. Experiments will be conducted to determine if aub protein interacts directly with these RNAs. Plans are described for cloning and characterizing the gene.

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 }}

Paul M. Macdonald其他文献

Translational regulation of maternal mRNAs.
母体 mRNA 的翻译调控。
aubergine enhances oskar translation in the Drosophila ovary.
茄子增强果蝇卵巢中的奥斯卡翻译。
  • DOI:
  • 发表时间:
    1996
  • 期刊:
  • 影响因子:
    4.6
  • 作者:
    Joan E. Wilson;Joanne E. Connell;Paul M. Macdonald
  • 通讯作者:
    Paul M. Macdonald
The Drosophila pumilio gene: an unusually long transcription unit and an unusual protein.
  • DOI:
  • 发表时间:
    1992
  • 期刊:
  • 影响因子:
    4.6
  • 作者:
    Paul M. Macdonald
  • 通讯作者:
    Paul M. Macdonald

Paul M. Macdonald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('Paul M. Macdonald', 18)}}的其他基金

Long noncoding RNA function in the Drosophila germ line
果蝇种系中的长非编码RNA功能
  • 批准号:
    9926897
  • 财政年份:
    2017
  • 资助金额:
    $ 19.27万
  • 项目类别:
Coordinating different steps in mRNA localization
协调 mRNA 定位的不同步骤
  • 批准号:
    9367001
  • 财政年份:
    2017
  • 资助金额:
    $ 19.27万
  • 项目类别:
Coordinating different steps in mRNA localization
协调 mRNA 定位的不同步骤
  • 批准号:
    10001543
  • 财政年份:
    2017
  • 资助金额:
    $ 19.27万
  • 项目类别:
Translational control by cis elements acting in trans
顺式元件作用于反式的翻译控制
  • 批准号:
    8325539
  • 财政年份:
    2011
  • 资助金额:
    $ 19.27万
  • 项目类别:
Translational control by cis elements acting in trans
顺式元件作用于反式的翻译控制
  • 批准号:
    8690910
  • 财政年份:
    2011
  • 资助金额:
    $ 19.27万
  • 项目类别:
Translational control by cis elements acting in trans
顺式元件作用于反式的翻译控制
  • 批准号:
    8064249
  • 财政年份:
    2011
  • 资助金额:
    $ 19.27万
  • 项目类别:
Translational control by cis elements acting in trans
顺式元件作用于反式的翻译控制
  • 批准号:
    8499375
  • 财政年份:
    2011
  • 资助金额:
    $ 19.27万
  • 项目类别:
Translational regulation of cellular morphogenesis in early Drosophila embryos
早期果蝇胚胎细胞形态发生的翻译调控
  • 批准号:
    7771696
  • 财政年份:
    2009
  • 资助金额:
    $ 19.27万
  • 项目类别:
Translational regulation of cellular morphogenesis in early Drosophila embryos
早期果蝇胚胎细胞形态发生的翻译调控
  • 批准号:
    8058746
  • 财政年份:
    2009
  • 资助金额:
    $ 19.27万
  • 项目类别:
Translational regulation of cellular morphogenesis in early Drosophila embryos
早期果蝇胚胎细胞形态发生的翻译调控
  • 批准号:
    8240453
  • 财政年份:
    2009
  • 资助金额:
    $ 19.27万
  • 项目类别:

相似海外基金

How lipid binding proteins shape the activity of nuclear hormone receptors
脂质结合蛋白如何影响核激素受体的活性
  • 批准号:
    DP240103141
  • 财政年份:
    2024
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Discovery Projects
Structural classification of NHEJ pathways; unravelling the role of Ku-binding proteins
NHEJ通路的结构分类;
  • 批准号:
    MR/X00029X/1
  • 财政年份:
    2023
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Research Grant
BRC-BIO: Evolutionary Patterns of Ice-Binding Proteins in North Pacific Intertidal Invertebrates
BRC-BIO:北太平洋潮间带无脊椎动物冰结合蛋白的进化模式
  • 批准号:
    2312378
  • 财政年份:
    2023
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Standard Grant
Exploring the roles and functions of sex steroid hormone receptor-associated RNA binding proteins in the development of geriatric diseases.
探索性类固醇激素受体相关 RNA 结合蛋白在老年疾病发展中的作用和功能。
  • 批准号:
    23K06408
  • 财政年份:
    2023
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
UV Plasmon-Enhanced Chiroptical Spectroscopy of Membrane-Binding Proteins
膜结合蛋白的紫外等离子增强手性光谱
  • 批准号:
    10680969
  • 财政年份:
    2023
  • 资助金额:
    $ 19.27万
  • 项目类别:
Investigating physiologic and pathophysiologic connections between the Parkinson's disease protein alpha-synuclein and RNA binding proteins
研究帕金森病蛋白 α-突触核蛋白和 RNA 结合蛋白之间的生理和病理生理联系
  • 批准号:
    10744556
  • 财政年份:
    2023
  • 资助金额:
    $ 19.27万
  • 项目类别:
Structural and computational analysis of immune-related RNA-binding proteins
免疫相关 RNA 结合蛋白的结构和计算分析
  • 批准号:
    23K06597
  • 财政年份:
    2023
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Characterization of carbohydrate-binding proteins and their applications
碳水化合物结合蛋白的表征及其应用
  • 批准号:
    23K05034
  • 财政年份:
    2023
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A machine learning approach to identify carbon dioxide-binding proteins for sustainability and health
一种机器学习方法来识别二氧化碳结合蛋白以实现可持续发展和健康
  • 批准号:
    2838427
  • 财政年份:
    2023
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Studentship
The role of RNA binding proteins in heart development and congenital heart defects
RNA结合蛋白在心脏发育和先天性心脏缺陷中的作用
  • 批准号:
    10827567
  • 财政年份:
    2023
  • 资助金额:
    $ 19.27万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了