The role of miR-128, a novel microRNA in somite development

miR-128（一种新型微小RNA）在体节发育中的作用

• 批准号: BB/K003437/1
• 负责人: Andrea Munsterberg
• 金额: $ 46.31万
• 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: 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%2FK003437%2F1
• 关键词: role; miR; 128; novel; microRNA

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 - they are told 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 are translated by a complex cellular machinery. Proteins are the 'movers and shakers' in a cell, they define a cell and they have specific jobs to do. For example, the contraction of skeletal muscle is mediated by fast and slow contractile fibers (made up of proteins). Muscle is a very plastic tissue and depending on whether you train to be a sprinter or a marathon runner different types of muscle proteins will be expressed. Muscle also has the ability to repair itself (to regenerate) for example after wearing a cast muscle mass is lost, but it builds up again quickly when the muscle is used again. We are interested in the molecules that control the development of muscle in an embryo, it is known that some of these factors are also used when muscle needs to regenerate, for example after injury or long-term bed rest. Our studies focus on a class of RNA molecules, which are not translated to make proteins. Here the RNA molecule itself has important functions. These non-coding RNAs were discovered recently and because they are very small, they were called 'micro'RNAs (miRs). They have been found in plants and animals, which means, that they are part of the most basic machinery of life with a very important and fundamental job to do in all cells - 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 an important novel function for a muscle specific microRNA in embryonic muscle. We also figured out how the production of the microRNA itself is being switched 'on' or 'off'. We identified the genes controlled by the microRNA (the 'targets') and we are beginning to understand how they in turn affect skeletal muscle. There are many additional microRNAs in developing muscle cells and we previously identified some of them using modern sequencing technology. We now want to understand what the role of these microRNAs is. Ideally we want to identify all the microRNAs and their target genes that play a role in skeletal muscle. Overall we will learn how an embryo makes normal, healthy, working muscle and this will in the long-term benefit people who suffer from various conditions that affect muscle health or help to alleviate age related muscle-loss.

多细胞生物体包含许多具有非常专门功能的不同细胞类型。例如，我们需要骨骼肌能够移动，而我们的皮肤可以防止脱水，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，受精卵。胚胎的发育始于卵子开始分裂产生许多细胞。不同的细胞在胚胎发育过程中被指定-它们被告知在早期胚胎中起作用的分子信号变成什么样。这些信号通常会导致特定的基因被“打开”或“关闭”。如果一个基因是“开”的，它就被表达，这意味着它是从细胞核中的DNA活跃地转录的。在转录过程中，DNA被复制成RNA。这些RNA转录物通常编码蛋白质，并由复杂的细胞机制翻译。蛋白质是细胞中的“推动者和震动者”，它们定义了一个细胞，它们有特定的工作要做。例如，骨骼肌的收缩是由快速和缓慢收缩纤维（由蛋白质组成）介导的。肌肉是一种可塑性很强的组织，取决于你是训练成为短跑运动员还是马拉松运动员，不同类型的肌肉蛋白会表达出来。肌肉也有自我修复（再生）的能力，例如在穿着石膏肌肉质量丢失后，但当肌肉再次使用时，它会迅速恢复。我们感兴趣的是控制胚胎中肌肉发育的分子，已知其中一些因素也用于肌肉需要再生时，例如受伤或长期卧床休息后。我们的研究集中在一类RNA分子上，它们不会被翻译成蛋白质。RNA分子本身具有重要的功能。这些非编码RNA是最近发现的，因为它们非常小，所以被称为“微小”RNA（miRs）。它们在植物和动物中被发现，这意味着它们是最基本的生命机制的一部分，在所有细胞中都有非常重要和基本的工作-事实上microRNA控制其他编码RNA是否被翻译成蛋白质。人们正在进行大量的研究，以帮助了解这是如何发生的，并揭示以这种方式控制的细胞过程的类型。我们的研究调查了细胞如何在发育中的脊椎动物胚胎中变得彼此不同。特别是，我们研究了控制细胞从多能前体分化为骨骼肌的决定的基因和分子，而不是例如骨骼。我们最近在胚胎肌肉中发现了一种肌肉特异性microRNA的重要新功能。我们还弄清楚了microRNA本身的产生是如何被“打开”或“关闭”的。我们确定了由microRNA控制的基因（“靶标”），我们开始了解它们如何反过来影响骨骼肌。在发育中的肌肉细胞中有许多额外的microRNA，我们以前使用现代测序技术鉴定了其中一些。我们现在想知道这些microRNA的作用是什么。理想情况下，我们希望确定所有在骨骼肌中发挥作用的microRNA及其靶基因。总的来说，我们将了解胚胎如何使正常，健康，工作的肌肉，这将在长期受益的人谁患有各种疾病，影响肌肉健康或帮助减轻年龄相关的肌肉损失。

项目成果

The Early Stages of Heart Development: Insights from Chicken Embryos.

• DOI: 10.3390/jcdd3020012
• 发表时间: 2016-04-05
• 期刊: Journal of cardiovascular development and disease
• 影响因子: 2.4
• 作者: Wittig JG;Münsterberg A
• 通讯作者: Münsterberg A

Fine-tuning of the PAX-SIX-EYA-DACH network by multiple microRNAs controls embryo myogenesis.

通过多种 microRNA 对 PAX-SIX-EYA-DACH 网络进行微调控制胚胎肌发生。

• DOI: 10.1016/j.ydbio.2020.10.005
• 发表时间: 2021
• 期刊: Developmental biology
• 影响因子: 2.7
• 作者: Viaut C

Investigating microRNA-target interactions during skeletal muscle development in chicken embryos

• 发表时间: 2017-05
• 作者: Camille Viaut

myomiR-dependent switching of BAF60 variant incorporation into Brg1 chromatin remodeling complexes during embryo myogenesis.

在胚胎肌发生过程中，BAF60变体掺入BAF60变体重塑络合物中的肌瘤依赖性切换。

• DOI: 10.1242/dev.108787
• 发表时间: 2014-09
• 期刊: Development (Cambridge, England)
• 作者: Goljanek-Whysall K;Mok GF;Fahad Alrefaei A;Kennerley N;Wheeler GN;Münsterberg A
• 通讯作者: Münsterberg A

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