title: Target mimicry provides a new mechanism for regulation of microRNA activity.
abstract: 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 cleavage. In plants, most miRNA targets are cleaved and show almost perfect complementarity with the miRNAs around the cleavage site. Here, we examined the non-protein coding gene IPS1 (INDUCED BY PHOSPHATE STARVATION 1) 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 content. 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.
authors.affiliation: Department of Plant Molecular Genetics, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Franco-Zorrilla
authors.forename: Adrián
authors.initials: A
authors.lastname: Valli
authors.forename: Marco
authors.initials: M
authors.lastname: Todesco
authors.forename: Isabel
authors.initials: I
authors.lastname: Mateos
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Puga
authors.forename: Ignacio
authors.initials: I
authors.lastname: Rubio-Somoza
authors.forename: Antonio
authors.initials: A
authors.lastname: Leyva
authors.forename: Detlef
authors.initials: D
authors.lastname: Weigel
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: García
authors.forename: Javier
authors.initials: J
authors.lastname: Paz-Ares
mesh_terms: D017360:Arabidopsis / Q000235:genetics* / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000235:genetics*; D018506:Gene Expression Regulation, Plant; D035683:MicroRNAs / Q000378:metabolism*; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000235:genetics* / Q000378:metabolism; D018749:RNA, Plant / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics*
chemical_list: D029681:Arabidopsis Proteins; D035683:MicroRNAs; D010940:Plant Proteins; D018749:RNA, Plant; C105499:phosphate starvation-induced protein 1, plant; C514696:UBC24 protein, Arabidopsis; D044763:Ubiquitin-Conjugating Enzymes