Target mimics: an embedded layer of microRNA-involved gene regulatory networks in plants

BackgroundMicroRNAs (miRNAs) play an essential role in gene regulation in plants. At the same time, the expression of miRNA genes is also tightly controlled. Recently, a novel mechanism called “target mimicry” was discovered, providing another layer for modulating miRNA activities. However, except for the artificial target mimics manipulated for functional studies on certain miRNA genes, only one example, IPS1 (Induced by Phosphate Starvation 1)—miR399 was experimentally confirmed in planta. To date, few analyses for comprehensive identification of natural target mimics have been performed in plants. Thus, limited evidences are available to provide detailed information for interrogating the questionable issue whether target mimicry was widespread in planta, and implicated in certain biological processes.ResultsIn this study, genome-wide computational prediction of endogenous miRNA mimics was performed in Arabidopsis and rice, and dozens of target mimics were identified. In contrast to a recent report, the densities of target mimic sites were found to be much higher within the untranslated regions (UTRs) when compared to those within the coding sequences (CDSs) in both plants. Some novel sequence characteristics were observed for the miRNAs that were potentially regulated by the target mimics. GO (Gene Ontology) term enrichment analysis revealed some functional insights into the predicted mimics. After degradome sequencing data-based identification of miRNA targets, the regulatory networks constituted by target mimics, miRNAs and their downstream targets were constructed, and some intriguing subnetworks were further exploited.ConclusionsThese results together suggest that target mimicry may be widely implicated in regulating miRNA activities in planta, and we hope this study could expand the current understanding of miRNA-involved regulatory networks.

[1]  Leonore Reiser,et al.  Huala, E. et al. The Arabidopsis Information Resource (TAIR): a comprehensive database and web-based information retrieval, analysis, and visualization system for a model plant. Nucleic Acids Res. 29, 102-105 , 2001 .

[2]  W. Pearson.  Searching protein sequence libraries: comparison of the sensitivity and selectivity of the Smith-Waterman and FASTA algorithms. , 1991, Genomics.

[3]  T. D. Schneider,et al.  Sequence logos: a new way to display consensus sequences. , 1990, Nucleic acids research.

[4]  Ping Wu,et al.  High-throughput degradome sequencing can be used to gain insights into microRNA precursor metabolism. , 2010, Journal of experimental botany.

[5]  Xuemei Chen,et al.  Small RNAs and their roles in plant development. , 2009, Annual review of cell and developmental biology.

[6]  Tao Liu,et al.  NONCODE v2.0: decoding the non-coding , 2007, Nucleic Acids Res..

[7]  M. Todesco,et al.  Target mimicry provides a new mechanism for regulation of microRNA activity , 2007, Nature Genetics.

[8]  Kan Nobuta,et al.  Plant MPSS databases: signature-based transcriptional resources for analyses of mRNA and small RNA , 2005, Nucleic Acids Res..

[9]  Hong Duan,et al.  The regulatory activity of microRNA* species has substantial influence on microRNA and 3′ UTR evolution , 2008, Nature Structural &Molecular Biology.

[10]  Dennis B. Troup,et al.  NCBI GEO: archive for high-throughput functional genomic data , 2008, Nucleic Acids Res..

[11]  O. Voinnet.  Origin, Biogenesis, and Activity of Plant MicroRNAs , 2009, Cell.

[12]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[13]  T. Nielsen,et al.  Dissecting the plant transcriptome and the regulatory responses to phosphate deprivation. , 2010, Physiologia plantarum.

[14]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[15]  Yuanji Zhang,et al.  miRU: an automated plant miRNA target prediction server , 2005, Nucleic Acids Res..

[16]  Gregory R. Heck,et al.  Regulation of Gene Expression in Plants through miRNA Inactivation , 2011, PloS one.

[17]  Neff Walker,et al.  A MicroRNA as a Translational Repressor of APETALA2 in Arabidopsis Flower Development , 2004 .

[18]  Wen Huang,et al.  The Arabidopsis Information Resource (TAIR): a comprehensive database and web-based information retrieval, analysis, and visualization system for a model plant , 2001, Nucleic Acids Res..

[19]  Ming Chen,et al.  Genome-wide survey of rice microRNAs and microRNA–target pairs in the root of a novel auxin-resistant mutant , 2009, Planta.

[20]  Sanghyuk Lee,et al.  MicroRNA genes are transcribed by RNA polymerase II , 2004, The EMBO journal.

[21]  D. Bartel,et al.  MicroRNAS and their regulatory roles in plants. , 2006, Annual review of plant biology.

[22]  S. Luo,et al.  Global identification of microRNA–target RNA pairs by parallel analysis of RNA ends , 2008, Nature Biotechnology.

[23]  Jia Liu,et al.  The TIGR rice genome annotation resource: annotating the rice genome and creating resources for plant biologists , 2003, Nucleic Acids Res..

[24]  Phillip D. Zamore,et al.  Sorting of Drosophila Small Silencing RNAs , 2007, Cell.

[25]  M. Stitt,et al.  PHO2, MicroRNA399, and PHR1 Define a Phosphate-Signaling Pathway in Plants1[W][OA] , 2006, Plant Physiology.

[26]  Tobias Dezulian,et al.  Sequence and expression differences underlie functional specialization of Arabidopsis microRNAs miR159 and miR319. , 2007, Developmental cell.

[27]  N. Chua,et al.  MicroRNA Directs mRNA Cleavage of the Transcription Factor NAC1 to Downregulate Auxin Signals for Arabidopsis Lateral Root Development , 2005, The Plant Cell Online.

[28]  Ming Chen,et al.  Toward microRNA-mediated gene regulatory networks in plants , 2011, Briefings Bioinform..

[29]  Yi Zhao,et al.  NONCODE: an integrated knowledge database of non-coding RNAs , 2004, Nucleic Acids Res..

[30]  Wei Li,et al.  Identification of drought-induced microRNAs in rice. , 2007, Biochemical and biophysical research communications.

[31]  Meng Zhao,et al.  Involvement of miR169 in the nitrogen-starvation responses in Arabidopsis. , 2011, The New phytologist.

[32]  G. Crooks,et al.  WebLogo: a sequence logo generator. , 2004, Genome research.

[33]  K. Shinozaki,et al.  TCP Transcription Factors Regulate the Activities of ASYMMETRIC LEAVES1 and miR164, as Well as the Auxin Response, during Differentiation of Leaves in Arabidopsis[C][W] , 2010, Plant Cell.

[34]  Patrick Xuechun Zhao,et al.  psRNATarget: a plant small RNA target analysis server , 2011, Nucleic Acids Res..

[35]  W R Pearson,et al.  Flexible sequence similarity searching with the FASTA3 program package. , 2000, Methods in molecular biology.

[36]  Pamela J Green,et al.  Construction of Parallel Analysis of RNA Ends (PARE) libraries for the study of cleaved miRNA targets and the RNA degradome , 2009, Nature Protocols.

[37]  Z. Weng,et al.  Sorting of Drosophila small silencing RNAs partitions microRNA* strands into the RNA interference pathway. , 2010, RNA.

[38]  Doron Betel,et al.  Widespread regulatory activity of vertebrate microRNA* species. , 2011, RNA.

[39]  Ming Chen,et al.  Construction of MicroRNA- and MicroRNA*-mediated regulatory networks in plants , 2011, RNA biology.

[40]  Detlef Weigel,et al.  A Collection of Target Mimics for Comprehensive Analysis of MicroRNA Function in Arabidopsis thaliana , 2010, PLoS genetics.

[41]  P. Laufs,et al.  The Balance between the MIR164A and CUC2 Genes Controls Leaf Margin Serration in Arabidopsis[W] , 2006, The Plant Cell Online.

[42]  Zhou Du,et al.  agriGO: a GO analysis toolkit for the agricultural community , 2010, Nucleic Acids Res..

[43]  Patrick Laufs,et al.  Co-ordination of developmental processes by small RNAs during leaf development. , 2010, Journal of experimental botany.

[44]  Ping Wu,et al.  PmiRKB: a plant microRNA knowledge base , 2010, Nucleic Acids Res..

[45]  M. Todesco,et al.  Interplay of SLIM1 and miR395 in the regulation of sulfate assimilation in Arabidopsis. , 2011, The Plant journal : for cell and molecular biology.

[46]  Hajime Sakai,et al.  Regulation of Flowering Time and Floral Organ Identity by a MicroRNA and Its APETALA2-Like Target Genes Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.016238. , 2003, The Plant Cell Online.

[47]  Patricia P. Chan,et al.  GtRNAdb: a database of transfer RNA genes detected in genomic sequence , 2008, Nucleic Acids Res..

[48]  Kazuki Saito,et al.  Sulphur starvation induces the expression of microRNA-395 and one of its target genes but in different cell types. , 2009, The Plant journal : for cell and molecular biology.

[49]  Masaaki Oda,et al.  QUMA: quantification tool for methylation analysis , 2008, Nucleic Acids Res..

[50]  Stijn van Dongen,et al.  miRBase: microRNA sequences, targets and gene nomenclature , 2005, Nucleic Acids Res..

[51]  Holger Hesse,et al.  Transcriptome analysis of sulfur depletion in Arabidopsis thaliana: interlacing of biosynthetic pathways provides response specificity. , 2003, The Plant journal : for cell and molecular biology.

[52]  Runzhi Li,et al.  UV-B-responsive microRNAs in Populus tremula. , 2009, Journal of plant physiology.