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Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression

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Listed:
  • Stephan Gehrke

    (Stanford University School of Medicine)

  • Yuzuru Imai

    (Institute of Development, Aging and Cancer, Tohoku University)

  • Nicholas Sokol

    (Indiana University)

  • Bingwei Lu

    (Stanford University School of Medicine)

Abstract

MicroRNAs in Parkinson's Mutations in leucine-rich repeat kinase 2 (LRRK2) have been linked to both familial and sporadic Parkinson's disease, but the biochemical function of LRRK2 has remained elusive. Now that function has been discovered. Both Drosophila and human LRRK2 are shown to antagonize microRNA-mediated translational inhibition of E2F1 and DP transcription factors. LRRK2 interacts with the RNA-induced silencing complex component Argonaute to antagonize its suppressive effect on protein translation. In vivo genetic studies demonstrate a key role for E2F1/DP upregulation in mediating mutant LRRK2 pathogenesis. These findings point to a link between impaired microRNA-mediated silencing and deregulated expression of specific microRNA targets to Parkinson's disease pathogenesis, and suggest possible microRNA-based therapeutic approaches.

Suggested Citation

  • Stephan Gehrke & Yuzuru Imai & Nicholas Sokol & Bingwei Lu, 2010. "Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression," Nature, Nature, vol. 466(7306), pages 637-641, July.
    • Handle: RePEc:nat:nature:v:466:y:2010:i:7306:d:10.1038_nature09191
    DOI: 10.1038/nature09191
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    1. Kasandra Burgos & Ivana Malenica & Raghu Metpally & Amanda Courtright & Benjamin Rakela & Thomas Beach & Holly Shill & Charles Adler & Marwan Sabbagh & Stephen Villa & Waibhav Tembe & David Craig & Ke, 2014. "Profiles of Extracellular miRNA in Cerebrospinal Fluid and Serum from Patients with Alzheimer's and Parkinson's Diseases Correlate with Disease Status and Features of Pathology," PLOS ONE, Public Library of Science, vol. 9(5), pages 1-20, May.

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