Potential roles of microRNAs in regulating long intergenic noncoding RNAs

BackgroundOver 10,000 long intergenic non-coding RNAs (lincRNAs) have been identified in the human genome. Some have been well characterized and known to participate in various stages of gene regulation. In the post-transcriptional process, another class of well-known small non-coding RNA, or microRNA (miRNA), is very active in inhibiting mRNA. Though similar features between mRNA and lincRNA have been revealed in several recent studies, and a few isolated miRNA-lincRNA relationships have been observed. Despite these advances, the comprehensive miRNA regulation pattern of lincRNA has not been clarified.MethodsIn this study, we investigated the possible interaction between the two classes of non-coding RNAs. Instead of using the existing long non-coding database, we employed an ab initio method to annotate lincRNAs expressed in a group of normal breast tissues and breast tumors.ResultsApproximately 90 lincRNAs show strong reverse expression correlation with miRNAs, which have at least one predicted target site presented. These target sites are statistically more conserved than their neighboring genetic regions and other predicted target sites. Several miRNAs that target to these lincRNAs are known to play an essential role in breast cancer.ConclusionSimilar to inhibiting mRNAs, miRNAs show potential in promoting the degeneration of lincRNAs. Breast-cancer-related miRNAs may influence their target lincRNAs resulting in differential expression in normal and malignant breast tissues. This implies the miRNA regulation of lincRNAs may be involved in the regulatory process in tumor cells.

[1]  Ana Kozomara,et al.  miRBase: integrating microRNA annotation and deep-sequencing data , 2010, Nucleic Acids Res..

[2]  Lior Pachter,et al.  Sequence Analysis , 2020, Definitions.

[3]  Nicholas T. Ingolia,et al.  Mammalian microRNAs predominantly act to decrease target mRNA levels , 2010, Nature.

[4]  K. Lindblad-Toh,et al.  Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals , 2005, Nature.

[5]  Wing Hung Wong,et al.  Identifiability of isoform deconvolution from junction arrays and RNA-Seq , 2009, Bioinform..

[6]  Manolis Kellis,et al.  Performance and Scalability of Discriminative Metrics for Comparative Gene Identification in 12 Drosophila Genomes , 2008, PLoS Comput. Biol..

[7]  Howard Y. Chang,et al.  Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes , 2010, Science.

[8]  S. K. Zaidi,et al.  MicroRNAs 221 and 222 bypass quiescence and compromise cell survival. , 2008, Cancer research.

[9]  Debora S. Marks,et al.  miRcode: a map of putative microRNA target sites in the long non-coding transcriptome , 2012, Bioinform..

[10]  Howard Y. Chang,et al.  Long intergenic noncoding RNAs: new links in cancer progression. , 2011, Cancer research.

[11]  J. Rinn,et al.  lincRNAs act in the circuitry controlling pluripotency and differentiation , 2011, Nature.

[12]  H. Horvitz,et al.  MicroRNA Expression in Zebrafish Embryonic Development , 2005, Science.

[13]  C. Burge,et al.  Most mammalian mRNAs are conserved targets of microRNAs. , 2008, Genome research.

[14]  Hui Xiao,et al.  NONCODE v3.0: integrative annotation of long noncoding RNAs , 2011, Nucleic Acids Res..

[15]  J. Rinn,et al.  Ab initio reconstruction of transcriptomes of pluripotent and lineage committed cells reveals gene structures of thousands of lincRNAs , 2010, Nature Biotechnology.

[16]  Paul T. Groth,et al.  The ENCODE (ENCyclopedia Of DNA Elements) Project , 2004, Science.

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

[18]  Beatrice Bodega,et al.  A Long ncRNA Links Copy Number Variation to a Polycomb/Trithorax Epigenetic Switch in FSHD Muscular Dystrophy , 2012, Cell.

[19]  Martin Reczko,et al.  The database of experimentally supported targets: a functional update of TarBase , 2008, Nucleic Acids Res..

[20]  J. Rinn,et al.  Large non-coding RNAs: missing links in cancer? , 2010, Human molecular genetics.

[21]  Manolis Kellis,et al.  New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes. , 2011, Genome research.

[22]  Colin N. Dewey,et al.  RNA-Seq gene expression estimation with read mapping uncertainty , 2009, Bioinform..

[23]  Kenneth P. Nephew,et al.  RNA Polymerase II Binding Patterns Reveal Genomic Regions Involved in MicroRNA Gene Regulation , 2010, PloS one.

[24]  Howard Y. Chang,et al.  Long noncoding RNA HOTAIR reprograms chromatin state to promote cancer metastasis , 2010, Nature.

[25]  J. Rinn,et al.  Ab initio reconstruction of transcriptomes of pluripotent and lineage committed cells reveals gene structures of thousands of lincRNAs , 2010, Nature biotechnology.

[26]  Kasie Rayman,et al.  The Center for Computational Biology and Bioinformatics , 2008 .

[27]  J. Mattick,et al.  Genome-wide analysis of long noncoding RNA stability , 2012, Genome research.

[28]  A. J. Schroeder,et al.  Revisiting the protein-coding gene catalog of Drosophila melanogaster using 12 fly genomes. , 2007, Genome research.

[29]  A. Barsotti,et al.  Noncoding RNAs: The Missing “Linc” in p53-Mediated Repression , 2010, Cell.

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

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

[32]  Daniel Herschlag,et al.  Systematic Identification of mRNAs Recruited to Argonaute 2 by Specific microRNAs and Corresponding Changes in Transcript Abundance , 2008, PloS one.

[33]  J. Rinn,et al.  A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response , 2010, Cell.

[34]  Paulo P. Amaral,et al.  Noncoding RNA in development , 2008, Mammalian Genome.

[35]  S. Nelson,et al.  BFAST: An Alignment Tool for Large Scale Genome Resequencing , 2009, PloS one.

[36]  J. Harrow,et al.  GENCODE: producing a reference annotation for ENCODE , 2006, Genome Biology.

[37]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[38]  M. Kiebler,et al.  Faculty Opinions recommendation of Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. , 2009 .

[39]  Cole Trapnell,et al.  Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. , 2010, Nature biotechnology.

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

[41]  Paul Ahlquist,et al.  MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins , 2008, Proceedings of the National Academy of Sciences.

[42]  John T. Wei,et al.  Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression , 2011, Nature Biotechnology.

[43]  Sam Griffiths-Jones,et al.  The microRNA Registry , 2004, Nucleic Acids Res..

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

[45]  Ahmad M. Khalil,et al.  Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs , 2012, Nucleic acids research.

[46]  C. Schoenherr,et al.  The Igf2/H19 imprinting control region exhibits sequence-specific and cell-type-dependent DNA methylation-mediated repression , 2008, Nucleic acids research.

[47]  James A. Cuff,et al.  Distinguishing protein-coding and noncoding genes in the human genome , 2007, Proceedings of the National Academy of Sciences.

[48]  M. Gerstein,et al.  Annotating non-coding regions of the genome , 2010, Nature Reviews Genetics.

[49]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[50]  Konstantin Khrapko,et al.  A microRNA array reveals extensive regulation of microRNAs during brain development. , 2003, RNA.

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

[52]  C. Croce,et al.  microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer , 2011, Oncogene.

[53]  Wing Hung Wong,et al.  Statistical inferences for isoform expression in RNA-Seq , 2009, Bioinform..

[54]  P. Fraser,et al.  No-Nonsense Functions for Long Noncoding RNAs , 2011, Cell.

[55]  R. Russell,et al.  bantam Encodes a Developmentally Regulated microRNA that Controls Cell Proliferation and Regulates the Proapoptotic Gene hid in Drosophila , 2003, Cell.

[56]  Aadel A. Chaudhuri,et al.  Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder , 2008, The Journal of experimental medicine.

[57]  Karissa Y. Sanbonmatsu,et al.  Structural architecture of the human long non-coding RNA, steroid receptor RNA activator , 2012, Nucleic acids research.

[58]  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.

[59]  N. Rajewsky,et al.  Widespread changes in protein synthesis induced by microRNAs , 2008, Nature.

[60]  Tom H. Pringle,et al.  The human genome browser at UCSC. , 2002, Genome research.

[61]  Yadong Wang,et al.  miR2Disease: a manually curated database for microRNA deregulation in human disease , 2008, Nucleic Acids Res..

[62]  Wayne Tam,et al.  Reticuloendotheliosis Virus Strain T Induces miR-155, Which Targets JARID2 and Promotes Cell Survival , 2009, Journal of Virology.

[63]  Michael Kertesz,et al.  The role of site accessibility in microRNA target recognition , 2007, Nature Genetics.

[64]  Jørgen Kjems,et al.  miRNA‐dependent gene silencing involving Ago2‐mediated cleavage of a circular antisense RNA , 2011, The EMBO journal.

[65]  Xiaohui Xie,et al.  Identifying novel constrained elements by exploiting biased substitution patterns , 2009, Bioinform..

[66]  Hiroyuki Tagawa,et al.  MicroRNA-17-92 down-regulates expression of distinct targets in different B-cell lymphoma subtypes. , 2008, Blood.