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.

多细胞生物包含许多具有非常特殊功能的不同细胞类型。例如，我们需要骨骼肌才能移动，而我们的皮肤可以防止脱水并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，胚胎的发育就开始了。不同的细胞在胚胎发育过程中被指定——通过早期胚胎中作用的分子信号告诉它们将变成什么。这些信号通常会导致特定基因“打开”或“关闭”。如果一个基因处于“开启”状态，它就会被表达，这意味着它在细胞核中从 DNA 中积极转录。在转录过程中，DNA 被复制成 RNA。这些 RNA 转录本通常编码蛋白质并由复杂的细胞机器翻译。蛋白质是细胞中的“推动者和摇动者”，它们定义了细胞，并且有特定的工作要做。例如，骨骼肌的收缩是由快收缩纤维和慢收缩纤维（由蛋白质组成）介导的。肌肉是一种可塑性很强的组织，根据您是否训练成为短跑运动员或马拉松运动员，会表达不同类型的肌肉蛋白。肌肉还具有自我修复（再生）的能力，例如在佩戴石膏后，肌肉质量会丢失，但当肌肉再次使用时，肌肉质量会迅速恢复。我们对控制胚胎中肌肉发育的分子感兴趣，众所周知，当肌肉需要再生时，例如受伤或长期卧床休息后，也会使用其中一些因子。我们的研究重点是一类 RNA 分子，它们不会被翻译来制造蛋白质。 RNA分子本身具有重要的功能。这些非编码 RNA 最近被发现，因为它们非常小，所以被称为“微小”RNA (miR)。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，在所有细胞中都承担着非常重要和基本的工作——事实上，microRNA 控制着其他编码 RNA 是否被翻译成蛋白质。正在进行大量研究，以帮助了解这是如何发生的，并揭示以这种方式控制什么类型的细胞过程。我们的研究调查了正在发育的脊椎动物胚胎中细胞如何变得彼此不同。特别是，我们研究控制细胞从多能前体分化成骨骼肌（而不是分化成骨骼）的决定的基因和分子。我们最近发现了胚胎肌肉中肌肉特异性 microRNA 的一个重要新功能。我们还弄清楚了 microRNA 本身的产生是如何“开启”或“关闭”的。我们确定了由 microRNA（“目标”）控制的基因，并且开始了解它们如何影响骨骼肌。发育中的肌肉细胞中还有许多额外的 microRNA，我们之前使用现代测序技术鉴定了其中一些。我们现在想要了解这些 microRNA 的作用是什么。理想情况下，我们希望识别在骨骼肌中发挥作用的所有 microRNA 及其靶基因。总的来说，我们将了解胚胎如何产生正常、健康、工作的肌肉，这将从长远来看使那些患有影响肌肉健康的各种疾病或有助于减轻与年龄相关的肌肉损失的人们受益。

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