alexa MicroRNA regulatory networks in cardiovascular development.
Genetics & Molecular Biology

Genetics & Molecular Biology

Human Genetics & Embryology

Author(s): Liu N, Olson EN

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Abstract The heart, more than any other organ, requires precise functionality on a second-to-second basis throughout the lifespan of the organism. Even subtle perturbations in cardiac structure or function have catastrophic consequences, resulting in lethal forms of congenital and adult heart disease. Such intolerance of the heart to variability necessitates especially robust regulatory mechanisms to govern cardiac gene expression. Recent studies have revealed central roles for microRNAs (miRNAs) as governors of gene expression during cardiovascular development and disease. The integration of miRNAs into the genetic circuitry of the heart provides a rich and robust array of regulatory interactions to control cardiac gene expression. miRNA regulatory networks also offer opportunities for therapeutically modulating cardiac function through the manipulation of pathogenic and protective miRNAs. We discuss the roles of miRNAs as regulators of cardiac form and function, unresolved questions in the field, and issues for the future. Copyright 2010 Elsevier Inc. All rights reserved.
This article was published in Dev Cell and referenced in Human Genetics & Embryology

Relevant Expert PPTs

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  • Yosef Yarden
    Classically, the 3’untranslated region (3’UTR) is that region in eukaryotic protein-coding genes from the translation termination codon to the polyA signal. It is transcribed as an integral part of the mRNA encoded by the gene. However, there exists another kind of RNA, which consists of the 3’UTR alone, without all other elements in mRNA such as 5’UTR and coding region. The importance of independent 3’UTR RNA (referred as I3’UTR) was prompted by results of artificially introducing such RNA species into malignant mammalian cells. Since 1991, we found that the middle part of the 3’UTR of the human nuclear factor for interleukin-6 (NF-IL6) or C/EBP gene exerted tumor suppression effect in vivo. Our subsequent studies showed that transfection of C/EBP 3’UTR led to down-regulation of several genes favorable for malignancy and to up-regulation of some genes favorable for phenotypic reversion. Also, it was shown that the sequences near the termini of the C/EBP 3’UTR were important for its tumor suppression activity. Then, the C/EBP 3’UTR was found to directly inhibit the phosphorylation activity of protein kinase CPKC in SMMC-7721, a hepatocarcinoma cell line. Recently, an AU-rich region in the C/EBP 3’UTR was found also to be responsible for its tumor suppression. Recently we have also found evidence that the independent C/EBP 3’UTR RNA is actually exists in human tissues, such as fetal liver and heart, pregnant uterus, senescent fibroblasts etc. Through 1990’s to 2000’s, world scientists found several 3’UTR RNAs that functioned as artificial independent RNAs in cancer cells and resulted in tumor suppression. Interestingly, majority of genes for these RNAs have promoter-like structures in their 3’UTR regions, although the existence of their transcribed products as independent 3’UTR RNAs is still to be confirmed. Our studies indicate that the independent 3’UTR RNA is a novel non-coding RNA species whose function should be the regulation not of the expression of their original mRNA, but of some essential life activities of the cell as a whole.
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  • Chuanling Zhang
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