（節(jié)選）外文翻譯--micrornas在肌肉發(fā)育中的作用（英文）

1、C H A P T E R T H R E EThe Role of MicroRNAs in Muscle DevelopmentNicholas S. SokolContents1. Introduction 602. Muscle miRNA Regulatory Networks 602.1. Identification of muscle miRNAs 602.2. Genomic organization of muscl

2、e miRNAs 612.3. Transcriptional control of muscle miRNAs 642.4. Posttranscriptional regulation of muscle miRNAs 642.5. mRNA targets of muscle miRNAs 653. Functional Analysis of miRNAs During Muscle Development 653.1. Mus

3、cle phenotypes of zebrafish and mouse dicer mutants 663.2. Muscle phenotypes of miRNA mutants 684. miRNAs in Muscle Stem Cells 735. Concluding Remarks 74References 75AbstractMicroRNAs play essential roles during animal d

4、evelopment, including in devel- oping muscle. Many microRNAs are expressed during muscle development and some, like miR-1 and miR-133, are muscle specific. Muscle microRNAs are integrated into myogenic regulatory network

5、s: their expression is under the transcriptional and posttranscriptional control of myogenic factors, and they in turn have widespread control of muscle gene expression. This review sum- marizes recent work characterizin

6、g the function of microRNAs in muscle biology and specifically focuses on the genetic analysis of muscle microRNAs in a variety of model organisms including worms, flies, zebrafish, and mice.Current Topics in Development

7、al Biology, Volume 99 # 2012 Elsevier Inc. ISSN 0070-2153, DOI: 10.1016/B978-0-12-387038-4.00003-3 All rights reserved.Department of Biology, Indiana University, Bloomington, Indiana, USA59(Aboobaker et al., 2005), and m

8、iR-133, -206, -216, and -499 in zebrafish (Kloosterman et al., 2006; Wienholds et al., 2005). Microarray analysis and deep sequencing experiments have significantly extended the number of miRNAs implicated in vertebrate

9、muscle develop- ment. These expression-profiling approaches have focused on identifying the complete repertoire of muscle miRNAs in embryonic and adult muscle tissue from diverse species (Huang et al., 2008; Li et al., 2

10、011). Microarray analysis of mouse tissue, for example, identified a total of 114 miRNAs that are expressed in the mouse heart, 25 of which are apparently heart specific (Tang et al., 2007). Subsequent deep sequencing of

11、 young adult mouse heart tissue found an enrichment of a small number of miRNAs, with miR-1 accounting for 40% of all cardiac miRNA expression (Rao et al., 2009). The level of miR-1 expression is striking: miR-1 is ?20-f

12、old more abundant than miR-208, a miRNA encoded within the intron of a cardiac myosin and therefore a reasonable proxy for a highly expressed cardiac mRNA. Other miRNAs enriched in heart tissues include members of the le

13、t-7, miR-26, miR-29, and miR-30 families. In a parallel approach to identify miRNAs involved in muscle biology, miRNA expression dynamics have been profiled in cultured mammalian cells undergoing skeletal or cardiac musc

14、le differentiation (Chen et al., 2006; Dey et al., 2011; Ivey et al., 2008; Naguibneva et al., 2006). For example, the expression of a collection of miRNAs including miR-1, -22, -26, -133, -181, -206, and -486 is upregul

15、ated as cultured murine C2C12 myoblasts differenti- ate into skeletal muscle (Chen et al., 2006; Dey et al., 2011; Naguibneva et al., 2006). Activation of these miRNAs may be required to promote differentia- tion program

16、s and is coincident with the downregulation of a second set of C2C12-expressedmiRNAsincluding miR-125b(Ge etal., 2011),whichlikely repress C2C12 differentiation. Indeed, an analogous role for miR-125b has recently been f

17、ound during skin cell differentiation, since miR-125b is highly expressed in skin progenitor cells and is sharply downregulated during their differentiation (Zhang et al., 2011). Similar profiling approaches have also be

18、en used to identify miRNAs involved in cardiac muscle differentiation. For example, 17 murine miR- NAs are upregulated as embryonic stem cells differentiate into cardiomyo- cytes, including miR-1, -133, -143, -182, -200,

19、 and -295 (Ivey et al., 2008). Taken together, these profiling analyses indicate that muscles have a rich palette of miRNAs that likely play myriad diverse roles during muscle development.2.2. Genomic organization of mus

20、cle miRNAsIn many animal genomes, muscle miRNAs are found clustered together (see Fig. 3.1). In both the mouse and human genomes, for example, each of the three members of the miR-1 family of miRNAs is located next to am