Contribution of ribosome specialization to the pathophysiology of muscular dystrophy

核糖体特化对肌营养不良症病理生理学的贡献

基本信息

  • 批准号:
    10685597
  • 负责人:
  • 金额:
    $ 11.7万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-08-17 至 2023-10-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract Striated muscle tissue contains the highest mitochondrial content and the largest known proteins, which present unique challenges to the translational machinery. Muscle tissue specifically expresses a paralogous ribosomal protein, RLP3L, that is roughly 80% similar to the ubiquitous RPL3, and is essential to the formation of the large subunit of the ribosome. In muscle, RPL3L substitutes for RPL3 in the ribosome, but how this alters ribosome function remains unknown. Furthermore, these two paralogs demonstrate an inverse relationship under conditions of muscle adaptation, stress, and pathology. In dystrophic muscle, RPL3L is lost in favor of RPL3 in the ribosome, but the effects on muscle functional decline are not understood. Recent evidence suggests that ribosomes can specialize in order to selectively translate certain genes into proteins. Additionally, translation control has emerged as a novel layer of regulation for mitochondrial function, which declines early in the pathology of muscular dystrophy, prior to an overt phenotype. Taken together, I hypothesize that the loss of RPL3L in dystrophic muscle impairs ribosome specialization, thus contributing to an imbalance between mitochondrial and sarcomeric protein synthesis, exacerbating dystrophic disease progression. Rescue of the muscle specific ribosomal protein in muscular dystrophy will provide the first evidence for a role of ribosome specialization in muscle functional decline, and help guide the design of new therapeutics. The proposed studies will also, for the first time, investigate the impact of glucocorticoids (a common therapy for dystrophy) on muscle ribosome specialization and translational selectivity. Successful completion of the proposed studies will reveal new therapeutic targets as well novel mechanisms underlying the pathophysiology of chronic debilitating diseases.
项目摘要/摘要 横纹肌组织含有最高的线粒体含量和已知最大的蛋白质, 这对翻译机器提出了独特的挑战。肌肉组织特异性地表达 一种类似的核糖体蛋白,RLP3L,与普遍存在的RPL3大约80%相似,是 核糖体大亚基的形成所必需的。在肌肉方面,RPL3L替代RPL3 在核糖体中,但这如何改变核糖体功能仍不清楚。此外,这两个人 在肌肉适应、压力和压力条件下,Paralog表现出相反的关系 病理学。在营养不良的肌肉中,RPL3L在核糖体中丢失而有利于RPL3,但对RPL3L的影响 肌肉功能衰退尚不清楚。最近的证据表明,核糖体可以 为了有选择地将某些基因翻译成蛋白质而专门研究。此外,平移控制 已经成为线粒体功能的一层新的调节层,线粒体功能在早期衰退 肌营养不良的病理学,在显性表型之前。综上所述,我假设 营养不良肌肉中RPL3L的丢失会损害核糖体的特化,从而导致失衡 线粒体和肌节蛋白合成之间的关系,加剧营养不良疾病 进步。在肌营养不良症中挽救肌肉特异性核糖体蛋白将提供 核糖体特化在肌肉功能衰退中的作用的第一个证据,并有助于指导 新疗法的设计。拟议的研究还将首次调查 糖皮质激素(治疗营养不良的常用疗法)对肌肉核糖体特化和 翻译选择性。拟议研究的成功完成将揭示新的治疗方法 目标以及慢性衰弱疾病的病理生理学基础的新机制。

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 }}

YUAN WEN其他文献

YUAN WEN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('YUAN WEN', 18)}}的其他基金

Contribution of ribosome specialization to the pathophysiology of muscular dystrophy
核糖体特化对肌营养不良症病理生理学的贡献
  • 批准号:
    10506115
  • 财政年份:
    2022
  • 资助金额:
    $ 11.7万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 11.7万
  • 项目类别:
    Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 11.7万
  • 项目类别:
    Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 11.7万
  • 项目类别:
    Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 11.7万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 11.7万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 11.7万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 11.7万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 11.7万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 11.7万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 11.7万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了