Molecular Functions of Long Non-Coding RNAs in Plants

The past decade has seen dramatic changes in our understanding of the scale and complexity of eukaryotic transcriptome owing to the discovery of diverse types of short and long non-protein-coding RNAs (ncRNAs). While short ncRNA-mediated gene regulation has been extensively studied and the mechanisms well understood, the function of long ncRNAs remains largely unexplored, especially in plants. Nevertheless, functional insights generated in recent studies with mammalian systems have indicated that long ncRNAs are key regulators of a variety of biological processes. They have been shown to act as transcriptional regulators and competing endogenous RNAs (ceRNAs), to serve as molecular cargos for protein re-localization and as modular scaffolds to recruit the assembly of multiple protein complexes for chromatin modifications. Some of these functions have been found to be conserved in plants. Here, we review our current understanding of long ncRNA functions in plants and discuss the challenges in functional characterization of plant long ncRNAs.

[1]  P. Pandolfi,et al.  A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language? , 2011, Cell.

[2]  Jeff Schell,et al.  Soybean ENOD40 encodes two peptides that bind to sucrose synthase , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Natalie de Souza Genomics: The ENCODE project , 2012, Nature Methods.

[4]  Howard Y. Chang,et al.  Molecular mechanisms of long noncoding RNAs. , 2011, Molecular cell.

[5]  Raymond K. Auerbach,et al.  Prediction and characterization of noncoding RNAs in C. elegans by integrating conservation, secondary structure, and high-throughput sequencing and array data. , 2011, Genome research.

[6]  M. Pellegrini,et al.  Genome-wide analysis of mono-, di- and trimethylation of histone H3 lysine 4 in Arabidopsis thaliana , 2009, Genome Biology.

[7]  G. Crabtree,et al.  Chromatin remodelling during development , 2010, Nature.

[8]  Yong Zhang,et al.  CPC: assess the protein-coding potential of transcripts using sequence features and support vector machine , 2007, Nucleic Acids Res..

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

[10]  V. Rubio,et al.  Influence of cytokinins on the expression of phosphate starvation responsive genes in Arabidopsis. , 2000, The Plant journal : for cell and molecular biology.

[11]  S. Burleigh,et al.  A novel gene whose expression in Medicago truncatula roots is suppressed in response to colonization by vesicular-arbuscular mycorrhizal (VAM) fungi and to phosphate nutrition , 1997, Plant Molecular Biology.

[12]  P. Zamore,et al.  Small silencing RNAs: an expanding universe , 2009, Nature Reviews Genetics.

[13]  Alessandro Guffanti,et al.  An Ariadne's thread to the identification and annotation of noncoding RNAs in eukaryotes , 2009, Briefings Bioinform..

[14]  Natalie de Souza The ENCODE project , 2012, Nature Methods.

[15]  Jeannie T. Lee,et al.  Polycomb Proteins Targeted by a Short Repeat RNA to the Mouse X Chromosome , 2008, Science.

[16]  Chun-Lin Su,et al.  Regulation of Phosphate Homeostasis by MicroRNA in Arabidopsis[W] , 2005, The Plant Cell Online.

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

[18]  C. Ponting,et al.  Evolution and Functions of Long Noncoding RNAs , 2009, Cell.

[19]  C. Dean,et al.  Cold-induced silencing by long antisense transcripts of an Arabidopsis Polycomb target , 2009, Nature.

[20]  M. J. Harrison,et al.  Loss of At4 function impacts phosphate distribution between the roots and the shoots during phosphate starvation. , 2006, The Plant journal : for cell and molecular biology.

[21]  H. Kouchi,et al.  Isolation and characterization of novel nodulin cDNAs representing genes expressed at early stages of soybean nodule development , 1993, Molecular and General Genetics MGG.

[22]  I. Goodhead,et al.  Dynamic repertoire of a eukaryotic transcriptome surveyed at single-nucleotide resolution , 2008, Nature.

[23]  C. Pikaard,et al.  Noncoding Transcription by RNA Polymerase Pol IVb/Pol V Mediates Transcriptional Silencing of Overlapping and Adjacent Genes , 2008, Cell.

[24]  Fatih Ozsolak,et al.  RNA sequencing: advances, challenges and opportunities , 2011, Nature Reviews Genetics.

[25]  Alexandra M. E. Jones,et al.  A PHD-Polycomb Repressive Complex 2 triggers the epigenetic silencing of FLC during vernalization , 2008, Proceedings of the National Academy of Sciences.

[26]  Ferdinando Di Cunto,et al.  Coding-Independent Regulation of the Tumor Suppressor PTEN by Competing Endogenous mRNAs , 2011, Cell.

[27]  M. Crespi,et al.  A novel RNA-binding peptide regulates the establishment of the Medicago truncatula-Sinorhizobium meliloti nitrogen-fixing symbiosis. , 2010, The Plant journal : for cell and molecular biology.

[28]  J. Mattick,et al.  Long non-coding RNAs: insights into functions , 2009, Nature Reviews Genetics.

[29]  K. Kinzler,et al.  The Antisense Transcriptomes of Human Cells , 2008, Science.

[30]  D. Chitwood,et al.  Small RNAs are on the move , 2010, Nature.

[31]  J. Ladha,et al.  Rice ENOD40: isolation and expression analysis in rice and transgenic soybean root nodules. , 1999, The Plant journal : for cell and molecular biology.

[32]  Graziano Pesole,et al.  Computational identification of protein coding potential of conserved sequence tags through cross-species evolutionary analysis. , 2003, Nucleic acids research.

[33]  T. Bisseling,et al.  Characterization of GmENOD40, a gene showing novel patterns of cell-specific expression during soybean nodule development. , 1993, The Plant journal : for cell and molecular biology.

[34]  S. Linnarsson,et al.  Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq. , 2011, Genome research.

[35]  P. Pandolfi,et al.  In Vivo Identification of Tumor- Suppressive PTEN ceRNAs in an Oncogenic BRAF-Induced Mouse Model of Melanoma , 2011, Cell.

[36]  K. Raghothama,et al.  Differential expression of TPS11, a phosphate starvation-induced gene in tomato , 1997, Plant Molecular Biology.

[37]  Stefan R. Henz,et al.  AGRONOMICS1: A New Resource for Arabidopsis Transcriptome Profiling1[W][OA] , 2009, Plant Physiology.

[38]  M. Crespi,et al.  Translational and Structural Requirements of the Early Nodulin Gene enod40, a Short-Open Reading Frame-Containing RNA, for Elicitation of a Cell-Specific Growth Response in the Alfalfa Root Cortex , 2001, Molecular and Cellular Biology.

[39]  C. Pleij,et al.  Structural motifs in the RNA encoded by the early nodulation gene enod40 of soybean. , 2003, Nucleic acids research.

[40]  Ming-Bo Wang,et al.  Alternate approaches to repress endogenous microRNA activity in Arabidopsis thaliana , 2011, Plant signaling & behavior.

[41]  Chun-Lin Su,et al.  pho2, a Phosphate Overaccumulator, Is Caused by a Nonsense Mutation in a MicroRNA399 Target Gene1[W] , 2006, Plant Physiology.

[42]  D. Cacchiarelli,et al.  A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA , 2011, Cell.

[43]  Martin Reczko,et al.  DIANA-EST: a statistical analysis , 2001, Bioinform..

[44]  A. Jacquier The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs , 2009, Nature Reviews Genetics.

[45]  Michael F. Lin,et al.  Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals , 2009, Nature.

[46]  Jae Bok Heo,et al.  Encoding memory of winter by noncoding RNAs , 2011, Epigenetics.

[47]  C. V. Jongeneel,et al.  Modeling sequencing errors by combining Hidden Markov models , 2003, ECCB.

[48]  O. Voinnet,et al.  Retracted: An endogenous, systemic RNAi pathway in plants , 2010, The EMBO journal.

[49]  S. Batalov,et al.  Antisense Transcription in the Mammalian Transcriptome , 2005, Science.

[50]  K. Shinozaki,et al.  Arabidopsis tiling array analysis to identify the stress-responsive genes. , 2010, Methods in molecular biology.

[51]  M. Crespi,et al.  Enod40, a Short Open Reading Frame–Containing mRNA, Induces Cytoplasmic Localization of a Nuclear RNA Binding Protein in Medicago truncatula , 2004, The Plant Cell Online.

[52]  Joseph M. Dale,et al.  Empirical Analysis of Transcriptional Activity in the Arabidopsis Genome , 2003, Science.

[53]  L Nyström,et al.  Statistical Analysis , 2008, Encyclopedia of Social Network Analysis and Mining.

[54]  Sibum Sung,et al.  Vernalization-Mediated Epigenetic Silencing by a Long Intronic Noncoding RNA , 2011, Science.

[55]  W. Scheible,et al.  MicroRNA399 is a long-distance signal for the regulation of plant phosphate homeostasis , 2008, The Plant journal : for cell and molecular biology.

[56]  S. Karlin,et al.  Finding the genes in genomic DNA. , 1998, Current opinion in structural biology.

[57]  Jennifer A. Mitchell,et al.  The Air Noncoding RNA Epigenetically Silences Transcription by Targeting G9a to Chromatin , 2008, Science.

[58]  G. Olsen,et al.  CRITICA: coding region identification tool invoking comparative analysis. , 1999, Molecular biology and evolution.

[59]  Peter Fraser,et al.  Emerging similarities in epigenetic gene silencing by long noncoding RNAs , 2009, Mammalian Genome.

[60]  John L Rinn,et al.  RNA traffic control of chromatin complexes. , 2010, Current opinion in genetics & development.

[61]  M. Osaki,et al.  Expression of the OsPI1 gene, cloned from rice roots using cDNA microarray, rapidly responds to phosphorus status , 2003 .

[62]  Yoichi Muraoka,et al.  Angle: a Sequencing Errors Resistant Program for Predicting Protein Coding Regions in Unfinished Cdna , 2006, J. Bioinform. Comput. Biol..

[63]  C. Bult,et al.  Transcript Annotation in FANTOM3: Mouse Gene Catalog Based on Physical cDNAs , 2006, PLoS genetics.

[64]  K. Rippe,et al.  Coding RNAs with a non-coding function: Maintenance of open chromatin structure , 2011, Nucleus.

[65]  Alexander P. Gultyaev,et al.  Identification of conserved secondary structures and expansion segments in enod40 RNAs reveals new enod40 homologues in plants , 2007, Nucleic acids research.

[66]  D. Wagner,et al.  Histone modifications and dynamic regulation of genome accessibility in plants. , 2007, Current opinion in plant biology.

[67]  P. Harrison,et al.  Mining Mammalian Transcript Data for Functional Long Non-Coding RNAs , 2010, PloS one.

[68]  Margaret S. Ebert,et al.  MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells , 2007, Nature Methods.

[69]  I. Henderson,et al.  Epigenetic inheritance in plants , 2007, Nature.

[70]  P. Pandolfi,et al.  A coding-independent function of gene and pseudogene mRNAs regulates tumour biology , 2010, Nature.

[71]  M. Borodovsky,et al.  GeneMark.hmm: new solutions for gene finding. , 1998, Nucleic acids research.

[72]  B. Williams,et al.  Mapping and quantifying mammalian transcriptomes by RNA-Seq , 2008, Nature Methods.

[73]  Pamela J Green,et al.  Diamonds in the rough: mRNA-like non-coding RNAs. , 2008, Trends in plant science.

[74]  S. Burleigh,et al.  The down-regulation of Mt4-like genes by phosphate fertilization occurs systemically and involves phosphate translocation to the shoots. , 1999, Plant physiology.

[75]  B. Blencowe,et al.  The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. , 2010, Molecular cell.

[76]  B. Graveley The developmental transcriptome of Drosophila melanogaster , 2010, Nature.

[77]  Ton Bisseling,et al.  ENOD40 expression in the pericycle precedes cortical cell division in Rhizobium-legume interaction and the highly conserved internal region of the gene does not encode a peptide , 2001, Plant and Soil.

[78]  M. Crespi,et al.  Novel long non-protein coding RNAs involved in Arabidopsis differentiation and stress responses. , 2008, Genome research.

[79]  Leonard Lipovich,et al.  Genome-wide computational identification and manual annotation of human long noncoding RNA genes. , 2010, RNA.

[80]  J. Rinn,et al.  Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression , 2009, Proceedings of the National Academy of Sciences.

[81]  Gaurav Kumar Pandey,et al.  Characterization of the RNA content of chromatin. , 2010, Genome research.

[82]  Sibum Sung,et al.  Environmentally coordinated epigenetic silencing of FLC by protein and long noncoding RNA components. , 2012, Current opinion in plant biology.

[83]  Takefumi Kondo,et al.  Coding vs non-coding: Translatability of short ORFs found in putative non-coding transcripts. , 2011, Biochimie.

[84]  B. Rost,et al.  Distinguishing Protein-Coding from Non-Coding RNAs through Support Vector Machines , 2006, PLoS genetics.

[85]  R. Amasino,et al.  FLOWERING LOCUS C Encodes a Novel MADS Domain Protein That Acts as a Repressor of Flowering , 1999, Plant Cell.

[86]  D. Buzas,et al.  Vernalization-Repression of Arabidopsis FLC Requires Promoter Sequences but Not Antisense Transcripts , 2011, PloS one.

[87]  Luigi Naldini,et al.  Stable knockdown of microRNA in vivo by lentiviral vectors , 2009, Nature Methods.

[88]  M. Robertson,et al.  The Arabidopsis thaliana vernalization response requires a polycomb-like protein complex that also includes VERNALIZATION INSENSITIVE 3 , 2006, Proceedings of the National Academy of Sciences.

[89]  Howard Y. Chang,et al.  Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs , 2007, Cell.

[90]  Cole Trapnell,et al.  Targeted RNA sequencing reveals the deep complexity of the human transcriptome , 2011, Nature Biotechnology.

[91]  S. Ranade,et al.  Stem cell transcriptome profiling via massive-scale mRNA sequencing , 2008, Nature Methods.

[92]  C. Wahlestedt,et al.  Regulatory roles of natural antisense transcripts , 2009, Nature Reviews Molecular Cell Biology.

[93]  Howard Y. Chang,et al.  Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. , 2011, Molecular cell.

[94]  Jian-Kang Zhu,et al.  A miRNA Involved in Phosphate-Starvation Response in Arabidopsis , 2005, Current Biology.

[95]  E. Heard,et al.  A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced. , 2006, Genes & development.

[96]  Jun Wang,et al.  Genome-wide transcription analyses in rice using tiling microarrays , 2006, Nature Genetics.

[97]  William Stafford Noble,et al.  Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project , 2007, Nature.

[98]  J. Komorowski,et al.  Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. , 2008, Molecular cell.

[99]  Toshiro K. Ohsumi,et al.  Genome-wide identification of polycomb-associated RNAs by RIP-seq. , 2010, Molecular cell.

[100]  M. Crespi,et al.  enod40 induces dedifferentiation and division of root cortical cells in legumes. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[101]  E. Dennis,et al.  Long non-coding RNA-mediated mechanisms independent of the RNAi pathway in animals and plants , 2011, RNA biology.

[102]  M. Crespi,et al.  enod40, a gene expressed during nodule organogenesis, codes for a non‐translatable RNA involved in plant growth. , 1994, The EMBO journal.

[103]  Edwards Allen,et al.  miRNAs in the biogenesis of trans-acting siRNAs in higher plants. , 2010, Seminars in cell & developmental biology.

[104]  Xuerui Yang,et al.  An Extensive MicroRNA-Mediated Network of RNA-RNA Interactions Regulates Established Oncogenic Pathways in Glioblastoma , 2011, Cell.

[105]  N. Nukina,et al.  RNA-Assisted Nuclear Transport of the Meiotic Regulator Mei2p in Fission Yeast , 1998, Cell.

[106]  W. Peacock,et al.  The FLF MADS Box Gene: A Repressor of Flowering in Arabidopsis Regulated by Vernalization and Methylation , 1999, Plant Cell.

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

[108]  Nick Goldman,et al.  RNAcode: robust discrimination of coding and noncoding regions in comparative sequence data. , 2011, RNA.

[109]  Vincenzo Pirrotta,et al.  Polycomb silencing mechanisms and the management of genomic programmes , 2007, Nature Reviews Genetics.