Letter abstract


Nature Genetics 39, 1033 - 1037 (2007)
Published online: 22 July 2007 | doi:10.1038/ng2079

Target mimicry provides a new mechanism for regulation of microRNA activity

José Manuel Franco-Zorrilla1, Adrián Valli1, Marco Todesco2, Isabel Mateos1, María Isabel Puga1, Ignacio Rubio-Somoza2, Antonio Leyva1, Detlef Weigel2, Juan Antonio García1 & Javier Paz-Ares1

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MicroRNAs (miRNA) regulate key aspects of development and physiology in animals and plants. These regulatory RNAs act as guides of effector complexes to recognize specific mRNA sequences based on sequence complementarity, resulting in translational repression or site-specific cleavage1, 2. In plants, most miRNA targets are cleaved and show almost perfect complementarity with the miRNAs around the cleavage site3, 4, 5, 6, 7, 8. Here, we examined the non–protein coding gene IPS1 (INDUCED BY PHOSPHATE STARVATION1) from Arabidopsis thaliana. IPS1 contains a motif with sequence complementarity to the phosphate (Pi) starvation–induced miRNA miR-399, but the pairing is interrupted by a mismatched loop at the expected miRNA cleavage site. We show that IPS1 RNA is not cleaved but instead sequesters miR-399. Thus, IPS1 overexpression results in increased accumulation of the miR-399 target PHO2 mRNA and, concomitantly, in reduced shoot Pi content5, 6, 7, 8. Engineering of IPS1 to be cleavable abolishes its inhibitory activity on miR-399. We coin the term 'target mimicry' to define this mechanism of inhibition of miRNA activity. Target mimicry can be generalized beyond the control of Pi homeostasis, as demonstrated using artificial target mimics.

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  1. Department of Plant Molecular Genetics, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain.
  2. Department of Molecular Biology, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.

Correspondence to: Javier Paz-Ares1 e-mail: jpazares@cnb.uam.es

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