Demonstrating polymorphic miRNA-mediated gene regulation in vivo: Application to the <i>g+6223G→A</i> mutation of Texel sheep

Takeda, Hitoshi; Charlier, Carole; Farnir, Frédéric; Georges, Michel

doi:10.1261/rna.2131110

Cited by 11 publications

(11 citation statements)

References 45 publications

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“…Although the 3′-UTR of a gene is typically thought of as not being as critical for its expression control as the coding and promoter regions, it does contain sequence elements affecting nuclear transport, polyadenylation, subcellular targeting, miRNA targeting, and stability of mRNA (65). However, mutations in the 3′-UTR have been shown to alter binding sites for miRNAs (319). Mutations in these sequences can therefore also influence gene transcription and translation.…”

Section: Identifying Genes Sequence Variants and Other Genomic Markersmentioning

confidence: 99%

Genomics and Genetics in the Biology of Adaptation to Exercise

Bouchard¹,

Rankinen²,

Timmons³

2011

Comprehensive Physiology

158

132

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This chapter is devoted to the role of genetic variation and gene-exercise interactions in the biology of adaptation to exercise. There is evidence from genetic epidemiology research that DNA sequence differences contribute to human variation in physical activity level, cardiorespiratory fitness in the untrained state, cardiovascular and metabolic response to acute exercise, and responsiveness to regular exercise. Methodological and technological advances have made it possible to undertake the molecular dissection of the genetic component of complex, multifactorial traits, such as those of interest to exercise biology, in terms of tissue expression profile, genes, and allelic variants. The evidence from animal models and human studies is considered. Data on candidate genes, genome-wide linkage results, genome-wide association findings, expression arrays, and combinations of these approaches are reviewed. Combining transcriptomic and genomic technologies has been shown to be more powerful as evidenced by the development of a recent molecular predictor of the ability to increase VO2max with exercise training. For exercise as a behavior and physiological fitness as a state to be major players in public health policies will require that that the role of human individuality and the influence of DNA sequence differences be understood. Likewise, progress in the use of exercise in therapeutic medicine will depend to a large extent on our ability to identify the favorable responders for given physiological properties to a given exercise regimen.

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Section: Identifying Genes Sequence Variants and Other Genomic Markersmentioning

confidence: 99%

Genomics and Genetics in the Biology of Adaptation to Exercise

Bouchard¹,

Rankinen²,

Timmons³

2011

Comprehensive Physiology

158

132

View full text Add to dashboard Cite

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“…Texel sheep carry a single mutation in the 3 -UTR of their myostatin gene, which is required to limit muscle growth [92]. This G→A point mutation creates a target site for both miR-1 and miR-206 [93] and makes myostatin susceptible to miRNA-mediated repression; this is sufficient to lead to a hypermuscled phenotype [93,94]. The biochemical methods used to identify this novel miRNA regulation are readily applicable and, in combination with highthroughput sequencing approaches, could be extended to systematically screen for common and rare SNPs (single nucleotide polymorphisms) that might affect target gene regulation by miRNAs.…”

Section: Animal Models Of Mirna Function In Muscle Growth and Developmentioning

confidence: 99%

microRNAs in skeletal muscle differentiation and disease

2012

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miRNAs (microRNAs) are novel post-transcriptional regulators of gene expression. Several miRNAs, expressed exclusively in muscle, play important roles during muscle development, growth and regeneration; other ubiquitously expressed miRNAs are also essential for muscle function. In the present review, we outline the miRNAs involved in embryonic muscle development and those that have been found to be dysregulated in diseases associated with skeletal muscle or are changed during muscle adaptation. miRNAs are promising biomarkers and candidates for potential therapeutic intervention. We discuss the strategies that aim to develop novel therapies through modulating miRNA activity. In time, some of these approaches may become available to treat muscle-associated diseases.

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“…It is worthwhile re-stating in this regard that miRNAs from the domain account for an estimated ;20% of cellular miRNAs in these animals. We are in the process of testing this prediction biochemically using both reporter assays and AGO-based (also known as EIF2C) target coimmunoprecipitation (e.g., Takeda et al 2010), prioritizing miRNAs on the basis of the results presented in Figure 4.…”

Section: Org Downloaded Frommentioning

confidence: 99%

Assessing the effect of the CLPG mutation on the microRNA catalog of skeletal muscle using high-throughput sequencing

et al. 2010

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The callipyge phenotype is a monogenic muscular hypertrophy that is only expressed in heterozygous sheep receiving the CLPG mutation from their sire. The wild-type phenotype of CLPG/CLPG animals is thought to result from translational inhibition of paternally expressed DLK1 transcripts by maternally expressed miRNAs. To identify the miRNA responsible for this trans effect, we used high-throughput sequencing to exhaustively catalog miRNAs expressed in skeletal muscle of sheep of the four CLPG genotypes. We have identified 747 miRNA species of which 110 map to the DLK1-GTL2 or callipyge domain. We demonstrate that the latter are imprinted and preferentially expressed from the maternal allele. We show that the CLPG mutation affects their level of expression in cis (;3.2-fold increase) as well as in trans (;1.8-fold increase). In CLPG/ CLPG animals, miRNAs from the DLK1-GTL2 domain account for ;20% of miRNAs in skeletal muscle. We show that the CLPG genotype affects the levels of A-to-I editing of at least five pri-miRNAs of the DLK1-GTL2 domain, but that levels of editing of mature miRNAs are always minor. We present suggestive evidence that the miRNAs from the domain target the ORF of DLK1, thereby causing the trans inhibition underlying polar overdominance. We highlight the limitations of high-throughput sequencing for digital gene expression profiling as a result of biased and inconsistent amplification of specific miRNAs.

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Demonstrating polymorphic miRNA-mediated gene regulation in vivo: Application to the g+6223G→A mutation of Texel sheep

Cited by 11 publications

References 45 publications

Genomics and Genetics in the Biology of Adaptation to Exercise

Genomics and Genetics in the Biology of Adaptation to Exercise

microRNAs in skeletal muscle differentiation and disease

Assessing the effect of the CLPG mutation on the microRNA catalog of skeletal muscle using high-throughput sequencing

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