Function of Tissue-specific eIF4E isoforms in Caenorhabditis elegans

胚胎发育中的关键问题是，“未分化的细胞如何改变特性，成为构成胎儿重要器官的特化细胞？”人们已经知道，在胚胎发育的非常早期，单个细胞中产生的新的和独特的蛋白质有助于它们具有成人组织类型的特征。引入(合成)新蛋白质的过程最终会引导细胞形成不同的器官系统，如大脑、肌肉、性腺和肠道。正是这种对胚胎中新蛋白质合成的调节是本研究的重点。土壤寄生线虫，秀丽线虫，从受精卵发育成有组织的多细胞胚胎，发育方式与高等动物非常相似。幸运的是，这些蠕虫的身体结构要简单得多，只由几块肌肉、神经元、消化和生殖器官组成。它们也会在一天内长成成年人。更重要的是，在这个简单的模型系统中，在发育最早阶段表达的关键基因和基因产物非常相似。这些产品中有信使RNA(信使RNA)，储存在鸡蛋或胚胎中。这些mRNAs在合适的时间被招募到核糖体(细胞的蛋白质合成机器)中，作为合成调节或结构蛋白质的模板。多年来，人们一直在研究信使核糖核酸的募集因子，并被认为在体内每种类型的细胞中都是相同的。然而，凯珀博士的实验室最近发现，在某些组织类型中发现了这些因子的独特形式(异构体)，最引人注目的是那些正在经历胚胎发育变化的组织。目前的项目解决了专门的蛋白质合成因子在选择哪些mRNAs用于胚胎细胞方面的作用。对它们独特活动的了解将开始揭示不同的细胞如何开始表达一组独特的蛋白质。这种特定于细胞的翻译控制是将胚胎从均匀的细胞团移植到复杂的成年生物体的内部程序的一部分。参与该项目的学生和博士后研究人员将学习信息生物分子(DNA、RNA和蛋白质)如何阐述使胚胎发生成为一个迷人的动态过程的变化。

The critical question in embryonic development is, "How do nondescript (undifferentiated) cells change in character to become the very specialized cells that make up the vital organs of a fetus?". It is already known that the production of new and unique proteins in individual cells very early in embryo development contributes to their taking on the character of adult tissue types. Processes that introduce (synthesize) new proteins ultimately direct cells to form distinct organ systems such as brain, muscle, gonad and gut. It is this regulation of new protein synthesis in embryos that is the focus of this research. The soil-dwelling nematode worm, Caenorhabditis elegans, develops from a fertilized egg to an organized multicellular embryo in a manner very similar to that of higher animals. Fortunately these worms have a far simpler body plan made up of just a few muscles, neurons, digestive and reproductive organs. They also grow to adulthood in just one day. More to the point, the critical genes and gene products expressed at the earliest stages of development are very similar in this simple model system. Among these products are messenger RNAs (mRNA) that are stored in egg or embryo. These mRNAs are recruited to ribosomes (the protein synthesizing machines of the cell) at just the right moment to be used as a template for the synthesis of regulatory or structural proteins. The mRNA recruiting factors have been studied for many years, and were thought to be identical in every type of cell in the body. However, Dr. Keiper's laboratory has recently shown that unique forms (isoforms) of these factors are found in certain tissue types, most notably those that are undergoing developmental changes in embryos. The current project addresses the role of specialized protein synthesis factors in selecting which mRNAs are used in embryonic cells. An understanding of their unique activities will begin to uncover how different cells begin to express a unique set of proteins. This cell-specific translational control is part of the internal program that takes embryos from a uniform mass of cells to a complex adult organism. Students and postdoctoral researchers involved in this project will learn how informational biomolecules (DNA, RNA and protein) elaborate the changes that make embryogenesis a fascinating dynamic process.