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Genetic variation and RNA structure regulate microRNA biogenesis

Author

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  • Noemi Fernandez

    (MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Genome Regulation Section, Western General Hospital, University of Edinburgh)

  • Ross A. Cordiner

    (MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Genome Regulation Section, Western General Hospital, University of Edinburgh)

  • Robert S. Young

    (MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Genome Regulation Section, Western General Hospital, University of Edinburgh)

  • Nele Hug

    (MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Genome Regulation Section, Western General Hospital, University of Edinburgh)

  • Sara Macias

    (MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Genome Regulation Section, Western General Hospital, University of Edinburgh
    Present address: Institute of Infection and Immunology Research, School of Biological Sciences, University of Edinburgh, King’s Buildings, Edinburgh EH9 3FL, UK)

  • Javier F. Cáceres

    (MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Genome Regulation Section, Western General Hospital, University of Edinburgh)

Abstract

MiRNA biogenesis is highly regulated at the post-transcriptional level; however, the role of sequence and secondary RNA structure in this process has not been extensively studied. A single G to A substitution present in the terminal loop of pri-mir-30c-1 in breast and gastric cancer patients had been previously described to result in increased levels of mature miRNA. Here, we report that this genetic variant directly affects Drosha-mediated processing of pri-mir-30c-1 in vitro and in cultured cells. Structural analysis of this variant revealed an altered RNA structure that facilitates the interaction with SRSF3, an SR protein family member that promotes pri-miRNA processing. Our results are compatible with a model whereby a genetic variant in pri-mir-30c-1 leads to a secondary RNA structure rearrangement that facilitates binding of SRSF3 resulting in increased levels of miR-30c. These data highlight that primary sequence determinants and RNA structure are key regulators of miRNA biogenesis.

Suggested Citation

  • Noemi Fernandez & Ross A. Cordiner & Robert S. Young & Nele Hug & Sara Macias & Javier F. Cáceres, 2017. "Genetic variation and RNA structure regulate microRNA biogenesis," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15114
    DOI: 10.1038/ncomms15114
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    Cited by:

    1. Bo Yu & Pan Li & Qiangfeng Cliff Zhang & Lin Hou, 2022. "Differential analysis of RNA structure probing experiments at nucleotide resolution: uncovering regulatory functions of RNA structure," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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