Target mimicry provides a new mechanism for regulation of microRNA activity Export

@article{citeulike:1477460, 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 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.}, address = {Department of Plant Molecular Genetics, Centro Nacional de Biotecnolog\'{\i}a, Consejo Superior de Investigaciones Cient\'{\i}ficas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain.}, author = {Franco-Zorrilla, Jose M. and Valli, Adrian and Todesco, Marco and Mateos, Isabel and Puga, Maria I. and Rubio-Somoza, Ignacio and Leyva, Antonio and Weigel, Detlef and Garcia, Juan A. and Paz-Ares, Javier}, citeulike-article-id = {1477460}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/ng2079}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/ng2079}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17643101}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17643101}, day = {22}, doi = {10.1038/ng2079}, issn = {1061-4036}, journal = {Nature Genetics}, keywords = {arabidopsis, microrna\_regulation, plants}, month = {July}, number = {8}, pages = {1033--1037}, posted-at = {2008-05-16 15:57:27}, priority = {2}, publisher = {Nature Publishing Group}, title = {Target mimicry provides a new mechanism for regulation of microRNA activity}, url = {http://dx.doi.org/10.1038/ng2079}, volume = {39}, year = {2007} }

TY - JOUR ID - citeulike:1477460 L3 - citeulike-article-id:1477460 N2 - 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. IS - 8 JF - Nature Genetics SN - 1061-4036 AD - Department of Plant Molecular Genetics, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain. EP - 1037 TI - Target mimicry provides a new mechanism for regulation of microRNA activity PB - Nature Publishing Group VL - 39 SP - 1033 KW - arabidopsis KW - microrna_regulation KW - plants AU - Franco-Zorrilla, Jose AU - Valli, Adrian AU - Todesco, Marco AU - Mateos, Isabel AU - Puga, Maria AU - Rubio-Somoza, Ignacio AU - Leyva, Antonio AU - Weigel, Detlef AU - Garcia, Juan AU - Paz-Ares, Javier PY - 2007/07/22/ UR - http://dx.doi.org/10.1038/ng2079 ER -