title: Systematic transcriptome wide analysis of lncRNA-miRNA interactions.
abstract: BACKGROUND
  Long noncoding RNAs (lncRNAs) are a recently discovered class of non-protein coding RNAs, which have now increasingly been shown to be involved in a wide variety of biological processes as regulatory molecules. The functional role of many of the members of this class has been an enigma, except a few of them like Malat and HOTAIR. Little is known regarding the regulatory interactions between noncoding RNA classes. Recent reports have suggested that lncRNAs could potentially interact with other classes of non-coding RNAs including microRNAs (miRNAs) and modulate their regulatory role through interactions. We hypothesized that lncRNAs could participate as a layer of regulatory interactions with miRNAs. The availability of genome-scale datasets for Argonaute targets across human transcriptome has prompted us to reconstruct a genome-scale network of interactions between miRNAs and lncRNAs.
  
  
  RESULTS
  We used well characterized experimental Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) datasets and the recent genome-wide annotations for lncRNAs in public domain to construct a comprehensive transcriptome-wide map of miRNA regulatory elements. Comparative analysis revealed that in addition to targeting protein-coding transcripts, miRNAs could also potentially target lncRNAs, thus participating in a novel layer of regulatory interactions between noncoding RNA classes. Furthermore, we have modeled one example of miRNA-lncRNA interaction using a zebrafish model. We have also found that the miRNA regulatory elements have a positional preference, clustering towards the mid regions and 3' ends of the long noncoding transcripts. We also further reconstruct a genome-wide map of miRNA interactions with lncRNAs as well as messenger RNAs.
  
  
  CONCLUSIONS
  This analysis suggests widespread regulatory interactions between noncoding RNAs classes and suggests a novel functional role for lncRNAs. We also present the first transcriptome scale study on miRNA-lncRNA interactions and the first report of a genome-scale reconstruction of a noncoding RNA regulatory interactome involving lncRNAs.
authors: GN Ramachandran Knowledge Center for Genome Informatics, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, India.
authors: Saakshi
authors: S
authors: Jalali
authors: Deeksha
authors: D
authors: Bhartiya
authors: Mukesh Kumar
authors: MK
authors: Lalwani
authors: Sridhar
authors: S
authors: Sivasubbu
authors: Vinod
authors: V
authors: Scaria
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D020869:Gene Expression Profiling / Q000379:methods*; D016678:Genome; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D059467:Transcriptome; D015027:Zebrafish / Q000235:genetics
chemical_list: C569474:MIRN125 microRNA, zebrafish; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger
references: Bioinformatics. 2011 Feb 1;27(3):431-2
references: 21149340
references: Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):2383-90
references: 22011751
references: PLoS Biol. 2004 Nov;2(11):e363
references: 15502875
references: Nucleic Acids Res. 2011 May;39(9):3864-78
references: 21247874
references: Bioinformatics. 2012 Aug 1;28(15):2062-3
references: 22718787
references: Nat Genet. 2007 Aug;39(8):1033-7
references: 17643101
references: J Genet Genomics. 2009 Jan;36(1):1-6
references: 19161940
references: Mol Cell. 2011 Dec 9;44(5):828-40
references: 22152485
references: Science. 2004 Oct 22;306(5696):636-40
references: 15499007
references: Nat Rev Genet. 2011 Jan;12(1):19-31
references: 21116305
references: Adv Exp Med Biol. 2011;722:59-74
references: 21915782
references: Nature. 2010 Oct 28;467(7319):1061-73
references: 20981092
references: Genome Biol. 2006;7 Suppl 1:S4.1-9
references: 16925838
references: Fly (Austin). 2009 Jul-Sep;3(3):204-6
references: 19556851
references: Nature. 2011 Feb 10;470(7333):187-97
references: 21307931
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D876-82
references: 20959295
references: Methods Mol Biol. 2009;546:227-40
references: 19378107
references: Nucleic Acids Res. 2010 Sep;38(16):5366-83
references: 20423907
references: Methods Cell Biol. 1999;59:117-26
references: 9891358
references: Genes Dev. 2009 Apr 1;23(7):862-76
references: 19293287
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D146-51
references: 21112873
references: Nat Rev Genet. 2009 Mar;10(3):155-9
references: 19188922
references: Bioinformatics. 2011 Sep 1;27(17):2325-9
references: 21697122
references: Int J Oncol. 2011 Jul;39(1):169-75
references: 21503572
references: Science. 2004 Apr 23;304(5670):594-6
references: 15105502
references: Prog Mol Biol Transl Sci. 2011;102:47-100
references: 21846569
references: Cell. 2011 Oct 14;147(2):358-69
references: 22000014
references: Anal Chim Acta. 2011 Aug 12;699(2):134-52
references: 21704768
references: Trends Genet. 2008 Jul;24(7):323-7
references: 18514357
references: Dev Biol. 2011 Sep 15;357(2):463-77
references: 21787766
references: Nat Rev Genet. 2011 Nov 18;12(12):861-74
references: 22094949
references: Nucleic Acids Res. 2008 Jan;36(Database issue):D154-8
references: 17991681
references: Biol Direct. 2012 Aug 07;7:25
references: 22871084
references: Nature. 2010 Apr 15;464(7291):1071-6
references: 20393566
references: PLoS One. 2012;7(12):e52588
references: 23285103
references: Brief Funct Genomic Proteomic. 2009 Nov;8(6):407-23
references: 19770204
references: World J Gastroenterol. 2009 May 7;15(17):2089-96
references: 19418581
references: Adv Exp Med Biol. 2011;722:1-19
references: 21915779
references: Physiol Rev. 2011 Jul;91(3):827-87
references: 21742789
references: RNA Biol. 2010 Sep-Oct;7(5):582-5
references: 20930520
references: Nat Rev Genet. 2009 Jan;10(1):57-63
references: 19015660
references: Cell. 2005 Nov 18;123(4):631-40
references: 16271387
references: PLoS Genet. 2010 Jul 22;6(7):e1001031
references: 20661442
references: Cell. 2011 Aug 5;146(3):353-8
references: 21802130
references: Retrovirology. 2006 Oct 11;3:68
references: 17032463
references: Cell. 2010 Apr 2;141(1):129-41
references: 20371350
references: Nucleic Acids Res. 2011 Feb;39(3):825-36
references: 20929877
references: Nucleic Acids Res. 2001 May 1;29(9):e45
references: 11328886
references: Protein Cell. 2010 Jun;1(6):520-36
references: 21204006
references: Curr Opin Mol Ther. 2010 Dec;12(6):684-94
references: 21154160
references: Expert Opin Drug Discov. 2012 Jun;7(6):503-13
references: 22559214
references: Plant Physiol. 2010 Sep;154(1):3-12
references: 20656899
references: Genome Res. 2008 Nov;18(11):1851-8
references: 18714091
references: FEBS Lett. 2005 Oct 31;579(26):5911-22
references: 16111679
references: Cell Cycle. 2010 Sep 1;9(17):3391-2
references: 20864820
references: Best Pract Res Clin Anaesthesiol. 2011 Dec;25(4):549-55
references: 22099920
references: BMC Genomics. 2007 Jun 07;8:152
references: 17555584
references: Nat Biotechnol. 2011 Jul 24;29(8):723-30
references: 21785424
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D105-10
references: 18996891
references: Hum Genet. 2011 Aug;130(2):223-36
references: 21626138
references: Retrovirology. 2007 Nov 24;4:82
references: 18036240
references: Science. 2005 May 6;308(5723):833-8
references: 15774722
references: Nucleic Acids Res. 2012 Nov 1;40(20):10018-31
references: 22923516
references: Methods Mol Biol. 2012;838:187-207
references: 22228013
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D152-7
references: 21037258