Genome-Wide Studies Reveal That Lin28 Enhances the Translation of Genes Important for Growth and Survival of Human Embryonic Stem Cells§

Authors

  • Shuping Peng,

    1. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA
    2. Yale Stem Cell Center, Yale University School of Medicine, New Haven, Connecticut, USA
    Current affiliation:
    1. Cancer Research Institute, Central South University, Hunan, People's Republica of China
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  • Ling-Ling Chen,

    1. Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut, USA
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  • Xin-Xiang Lei,

    1. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA
    2. Department of Chemistry, Wenzhou University, Zhejiang, People's Republic of China
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  • Li Yang,

    1. Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut, USA
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  • Haifan Lin,

    1. Yale Stem Cell Center, Yale University School of Medicine, New Haven, Connecticut, USA
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  • Gordon G. Carmichael,

    1. Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut, USA
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  • Yingqun Huang

    Corresponding author
    1. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA
    2. Yale Stem Cell Center, Yale University School of Medicine, New Haven, Connecticut, USA
    • Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA
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    • Telephone: 203-737-2578; Fax: 203-785-7134


  • Disclosure of potential conflicts of interest is found at the end of this article.

  • Author contributions: S.P.: collection and assembly of data, data analysis and interpretation; L.-L.C.: data analysis and interpretation, financial support; X.-X.L.: collection and assembly of data; L.Y.: data analysis and interpretation; H.L.: conception and design, financial support; G.G.C.: conception and design, financial support; Y.H.: conception and design, data analysis and interpretation, financial support.

  • §

    First published online in STEM CELLSEXPRESS January 7, 2011.

Abstract

Lin28 inhibits the expression of let-7 microRNAs but also exhibits let-7-independent functions. Using immunoprecipitation and deep sequencing, we show here that Lin28 preferentially associates with a small subset of cellular mRNAs. Of particular interest are those for ribosomal proteins and metabolic enzymes, the expression levels of which are known to be coupled to cell growth and survival. Polysome profiling and reporter analyses suggest that Lin28 stimulates the translation of many or most of these targets. Moreover, Lin28-responsive elements were found within the coding regions of all target genes tested. Finally, a mutant Lin28 that still binds RNA but fails to interact with RNA helicase A (RHA), acts as a dominant-negative inhibitor of Lin28-dependent stimulation of translation. We suggest that Lin28, working in concert with RHA, enhances the translation of genes important for the growth and survival of human embryonic stem cells. STEM CELLS 2011;496–504

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