The role of microRNAs miR206 and miR133 in somite development and myogenesis

microRNA miR206 和 miR133 在体节发育和肌生成中的作用

• 批准号: BB/D016444/1
• 负责人: Andrea Munsterberg
• 金额: $ 43.8万
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD016444%2F1
• 关键词: role; microRNAs; miR206; miR133; somite

Multi-cellular organisms contain many distinct cell types with very specialized functions. For example, we need skeletal muscle to be able to move while our skin prevents dehydration and protects us from injury and infections. Amazingly all these different cells arise from a single cell, the fertilized egg. The development of an embryo begins when the egg starts dividing to give rise to many cells. Different cells are specified during embryonic development. This means that they are essentially told what to do and what to become by molecular signals that act in the early embryo. These signals often cause specific genes to be switched 'on' or 'off'. If a gene is 'on' it is expressed which means that it is actively transcribed from the DNA in the nucleus of the cell. During the process of transcription, DNA is copied into RNA. These RNA transcripts typically encode proteins and RNA is translated into proteins by a complex cellular machinery. Proteins are the 'movers and shakers' in a cell and they have specific jobs to do. For example, they control the processes of transcription and translation and therefore help to make more proteins. Proteins are also an important part of the building blocks of a cell, for example, the contractile fibres of a muscle cells or the rigid cytoskeleton of a skin cell. However, not all RNA is translated to make protein and the RNA molecule itself can have important functions. A new class of these non-coding RNAs was discovered recently. Because this class of RNAs is very small, they were called microRNAs. They have been found in plants and animals, which means, that they are most likely part of the most basic machinery of life with a very important and fundamental job to do in all cells. This turned out to be the case and in fact microRNAs control whether or not other coding RNAs are translated into protein. A lot of research is being done, to help understand how this is happening and to uncover what type of cellular processes are controlled in this fashion. Our research investigates how cells become different from one another in a developing vertebrate embryo. In particular, we study the genes and molecules that control the decision of a cell to differentiate into skeletal muscle from a multi-potent precursor, as opposed to into bone for example. We recently discovered that two of these new microRNAs (and there are currently more than 200 microRNAs known) are only present in those cells in the embryo, that will go on to make skeletal muscle and we want to understand what the role of these microRNAs is. This includes to figure out how the production of the microRNA itself is being switched 'on' or 'off', and to identify which other genes are controlled by the microRNAs. Overall we will learn how an embryo makes normal, healthy, working muscle and this will in the long-term benefit patients who suffering from various muscle degenerative diseases.

多细胞生物包含许多不同的细胞类型，具有非常特殊的功能。例如，我们需要骨骼肌能够移动，同时我们的皮肤防止脱水，保护我们免受伤害和感染。令人惊讶的是，所有这些不同的细胞都来自一个细胞，即受精卵。当卵子开始分裂产生许多细胞时，胚胎就开始发育。不同的细胞在胚胎发育过程中是特定的。这意味着他们基本上被告知通过在早期胚胎中作用的分子信号来做什么和成为什么。这些信号通常会导致特定基因被“开启”或“关闭”。如果一个基因是“开”的，它就会被表达，这意味着它是从细胞核中的DNA活跃地转录出来的。在转录过程中，DNA被复制到RNA中。这些RNA转录本通常编码蛋白质，RNA通过复杂的细胞机器翻译成蛋白质。蛋白质是细胞中的“推动者和摇摆者”，它们有特定的工作要做。例如，它们控制转录和翻译的过程，因此有助于制造更多的蛋白质。蛋白质也是细胞构件的重要组成部分，例如肌肉细胞的收缩纤维或皮肤细胞的刚性细胞骨架。然而，并不是所有的RNA都被翻译成蛋白质，RNA分子本身可能具有重要的功能。最近发现了一类新的非编码RNA。因为这类RNA非常小，所以它们被称为microRNAs。它们已经在植物和动物中被发现，这意味着它们很可能是最基本的生命机械的一部分，在所有细胞中都有非常重要和基本的工作。事实证明是这样的，事实上，microRNAs控制着其他编码RNA是否被翻译成蛋白质。许多研究正在进行，以帮助理解这种情况是如何发生的，并揭示哪些类型的细胞过程是以这种方式控制的。我们的研究调查了在发育中的脊椎动物胚胎中，细胞如何变得不同。特别是，我们研究了控制细胞从多潜能前体分化为骨骼肌的决定的基因和分子，而不是例如分化为骨骼的决定。我们最近发现，其中两个新的microRNAs(目前已知的有200多个microRNAs)只存在于胚胎中的那些细胞中，这些细胞将继续形成骨骼肌，我们想要了解这些microRNAs的作用是什么。这包括弄清楚microRNA本身的生产是如何被“开启”或“关闭”的，以及识别哪些其他基因受microRNA控制。总体而言，我们将学习胚胎如何形成正常、健康、工作的肌肉，这将使患有各种肌肉退行性疾病的患者长期受益。

项目成果

The coordinated regulation of BAF60 variants by miR-1/206 and miR-133 clusters stabilises myogenic differentiation during embryogenesis

miR-1/206 和 miR-133 簇对 BAF60 变体的协调调节可稳定胚胎发生过程中的生肌分化

• 发表时间: 2015
• 期刊: INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY
• 影响因子: 3
• 作者: Goljanek-Whysall K.

A Database of microRNA Expression Patterns in Xenopus laevis.

• DOI: 10.1371/journal.pone.0138313
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Ahmed A;Ward NJ;Moxon S;Lopez-Gomollon S;Viaut C;Tomlinson ML;Patrushev I;Gilchrist MJ;Dalmay T;Dotlic D;Münsterberg AE;Wheeler GN
• 通讯作者: Wheeler GN

Detailed expression profile of all six Glypicans and their modifying enzyme Notum during chick embryogenesis and their role in dorsal-ventral patterning of the neural tube.

鸡胚胎发生过程中所有六种磷脂酰肌醇蛋白聚糖及其修饰酶 Notum 的详细表达谱及其在神经管背腹模式中的作用。

• DOI: 10.1016/j.gene.2017.01.032
• 发表时间: 2017
• 期刊: Gene
• 影响因子: 3.5
• 作者: Saad K