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Elucidating the molecular and biological functions of mammalian-specific PABP5, a unique non-canonical PABP.

阐明哺乳动物特异性 PABP5（一种独特的非典型 PABP）的分子和生物学功能。

基本信息

批准号：
BB/J01687X/1
负责人：
Nicola Gray
金额：
$ 67.66万
依托单位：
University of Edinburgh
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2013
资助国家：
英国
起止时间：
2013 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FJ01687X%2F1
关键词：
Elucidating molecular biological functions mammalian

项目摘要

The proteins that make up our cells are encoded by genes that serve as a genetic blueprint. The information stored in genes is expressed, or decoded, to produce proteins by a multi-step process known as gene expression. In this process, the genes within DNA are first converted to mRNA, which is used as a template to make proteins. This latter step is known as mRNA translation. In order to function properly, cells and organisms need to make proteins at the right time, place and in the correct amount. Thus it is critical that mRNA translation is carefully regulated, with improper control leading to a wide variety of diseases including cancer, metabolic, neurological and reproductive disorders. Regulating translation is also critical to industrial processes that require the efficient synthesis of particular proteins.Poly(A)-binding protein (PABP) 1 is a central regulator of multiple steps in the gene expression pathway, including mRNA translation. Mammals contain five genes belonging to the PABP family, including PABP5. PABP5 is only found in mammals and because it does not closely resemble the other PABPs, its function has remained enigmatic. In fact, its dissimilarity raises the possibility that PABP5 may have a unique and essential function in mammals. Interestingly in this regard, limited studies in patients with genetic abnormalities have raised the possibility that improper function of PABP5 could be linked to specific cases of mental retardation or premature ovarian failure. The latter is a condition where young women run out of eggs at an early age leading to infertility and osteoporosis. Critically, we have recently started to probe the function of PABP5, establishing that it does not share the functions of the classical PABP proteins. This supports our idea that PABP5 has a novel role in regulating mRNAs in mammals. Thus the research in this proposal aims to elucidate the molecular functions of PABP5 by exploring its ability to regulate different aspects of mRNA translation. Potential roles in mRNA stability will also be examined, as the destruction of mRNAs is often closely linked to their translation. This analysis will be complemented by the identification of the mRNAs within cells that are controlled by PABP5 and by an exploration of its biological roles. Taken together these experiments should provide unique insight into this novel regulator of protein synthesis and shed light on its potential roles in human and animal health. In conclusion, this project will increase our understanding of the critical mechanisms that regulate gene expression to ensure the proper functioning of cells within the body. Understanding such fundamental regulatory mechanisms forms an important and necessary step towards intervention aimed at improving human or animal health or towards industrial innovation.

构成我们细胞的蛋白质是由作为遗传蓝图的基因编码的。储存在基因中的信息被表达或解码，通过一个称为基因表达的多步骤过程来产生蛋白质。在这个过程中，DNA中的基因首先被转化为信使核糖核酸，作为制造蛋白质的模板。后一步称为信使核糖核酸翻译。为了正常运作，细胞和生物体需要在正确的时间、地点和正确的数量制造蛋白质。因此，仔细调控信使核糖核酸的翻译是至关重要的，不恰当的调控会导致多种疾病，包括癌症、新陈代谢、神经和生殖障碍。在需要有效合成特定蛋白质的工业过程中，调节翻译也是至关重要的。聚(A)结合蛋白(PABP)1是基因表达途径中多个步骤的中央调节因子，包括mRNA翻译。哺乳动物包含五个属于PABP家族的基因，包括PABP5。PABP5只在哺乳动物中发现，由于它与其他PABPs不太相似，其功能仍然是个谜。事实上，它的不同增加了PABP5可能在哺乳动物中具有独特和必要的功能的可能性。有趣的是，对遗传异常患者的有限研究提出了PABP5功能异常可能与特定的智力低下或卵巢早衰有关的可能性。后者是一种情况，年轻女性在很小的时候就会用完卵子，导致不孕和骨质疏松。关键的是，我们最近开始探索PABP5的功能，确定它不具有经典的PABP蛋白的功能。这支持了我们的观点，即PABP5在调节哺乳动物mRNAs方面具有新的作用。因此，本研究旨在通过研究PABP5调控mRNA翻译的不同方面来阐明PABP5的分子功能。还将研究在mRNA稳定性中的潜在作用，因为mRNAs的破坏通常与它们的翻译密切相关。这一分析将通过鉴定受PABP5控制的细胞内的mRNAs和探索其生物学作用来补充。综上所述，这些实验应该为这种新的蛋白质合成调节因子提供独特的见解，并阐明其在人类和动物健康中的潜在作用。总而言之，这个项目将增加我们对调节基因表达以确保体内细胞正常运作的关键机制的理解。了解这些基本的监管机制是朝着旨在改善人类或动物健康或工业创新的干预措施迈出的重要和必要的一步。