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

构成我们细胞的蛋白质是由基因编码的，这些基因充当着基因蓝图的角色。储存在基因中的信息被表达或解码，通过一个被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mRNA， mRNA被用作制造蛋白质的模板。后一个步骤被称为mRNA翻译。为了正常运作，细胞和有机体需要在正确的时间、地点和数量上制造蛋白质。因此，仔细调节mRNA的翻译是至关重要的，如果控制不当，就会导致各种各样的疾病，包括癌症、代谢、神经和生殖疾病。调节翻译对于需要有效合成特定蛋白质的工业过程也至关重要。聚(A)结合蛋白（PABP） 1是基因表达途径中多个步骤的中心调控因子，包括mRNA翻译。哺乳动物含有5个PABP家族基因，其中包括PABP5。PABP5仅在哺乳动物中发现，由于它与其他PABPs不太相似，它的功能仍然是个谜。事实上，它的差异性提出了PABP5可能在哺乳动物中具有独特而重要的功能的可能性。有趣的是，在这方面，对遗传异常患者的有限研究提出了PABP5功能异常可能与智力迟钝或卵巢早衰的特定病例有关的可能性。后者是指年轻女性在年轻时耗尽卵子，导致不孕症和骨质疏松症。关键的是，我们最近开始探索PABP5的功能，确定它不共享经典PABP蛋白的功能。这支持了我们的观点，即PABP5在哺乳动物mrna调节中具有新的作用。因此，本课题的研究旨在通过探究PABP5调控mRNA翻译不同方面的能力来阐明其分子功能。在mRNA稳定性中的潜在作用也将被研究，因为mRNA的破坏通常与它们的翻译密切相关。这一分析将通过鉴定细胞内受PABP5控制的mrna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剂提供独特的见解，并阐明其在人类和动物健康中的潜在作用。总之，这个项目将增加我们对调节基因表达的关键机制的理解，以确保体内细胞的正常功能。了解这些基本的管理机制是朝着旨在改善人类或动物健康或实现工业创新的干预迈出的重要和必要的一步。

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.