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Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis

Author

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  • Yong Zhao

    (Department of Pediatrics (Cardiology)
    University of Texas Southwestern Medical Center and Children's Medical Center Dallas
    University of California San Francisco)

  • Eva Samal

    (Department of Pediatrics (Cardiology)
    University of Texas Southwestern Medical Center and Children's Medical Center Dallas
    University of California San Francisco)

  • Deepak Srivastava

    (Department of Pediatrics (Cardiology)
    University of Texas Southwestern Medical Center and Children's Medical Center Dallas
    University of California San Francisco)

Abstract

Gradients of signalling and transcription factors govern many aspects of embryogenesis, highlighting the need for spatiotemporal control of regulatory protein levels. MicroRNAs are phylogenetically conserved small RNAs that regulate the translation of target messenger RNAs, providing a mechanism for protein dose regulation. Here we show that microRNA-1-1 (miR-1-1) and miR-1-2 are specifically expressed in cardiac and skeletal muscle precursor cells. We found that the miR-1 genes are direct transcriptional targets of muscle differentiation regulators including serum response factor, MyoD and Mef2. Correspondingly, excess miR-1 in the developing heart leads to a decreased pool of proliferating ventricular cardiomyocytes. Using a new algorithm for microRNA target identification that incorporates features of RNA structure and target accessibility, we show that Hand2, a transcription factor that promotes ventricular cardiomyocyte expansion, is a target of miR-1. This work suggests that miR-1 genes titrate the effects of critical cardiac regulatory proteins to control the balance between differentiation and proliferation during cardiogenesis.

Suggested Citation

  • Yong Zhao & Eva Samal & Deepak Srivastava, 2005. "Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis," Nature, Nature, vol. 436(7048), pages 214-220, July.
    • Handle: RePEc:nat:nature:v:436:y:2005:i:7048:d:10.1038_nature03817
    DOI: 10.1038/nature03817
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    Cited by:

    1. E. Juszczuk-Kubiak & K. Wicińska & J. Oprządek, 2013. "Association of novel polymorphisms in the bovine myocyte enhancer factor 2D (MEF2D) gene with carcass traits of Polish Holstein-Friesian cattle," Czech Journal of Animal Science, Czech Academy of Agricultural Sciences, vol. 58(6), pages 262-269.
    2. Parawee Lekprasert & Michael Mayhew & Uwe Ohler, 2011. "Assessing the Utility of Thermodynamic Features for microRNA Target Prediction under Relaxed Seed and No Conservation Requirements," PLOS ONE, Public Library of Science, vol. 6(6), pages 1-13, June.
    3. Thuc Duy Le & Junpeng Zhang & Lin Liu & Jiuyong Li, 2015. "Ensemble Methods for MiRNA Target Prediction from Expression Data," PLOS ONE, Public Library of Science, vol. 10(6), pages 1-19, June.
    4. Xiaomin Ying & Yuan Cao & Jiayao Wu & Qian Liu & Lei Cha & Wuju Li, 2011. "sTarPicker: A Method for Efficient Prediction of Bacterial sRNA Targets Based on a Two-Step Model for Hybridization," PLOS ONE, Public Library of Science, vol. 6(7), pages 1-12, July.

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