Skip to content
naulon
Get started

No retraction, correction or concern found when last checked on Oct 31, 2026.

Systematic Transcriptome Wide Analysis of lncRNA-miRNA Interactions

Saakshi Jalali, Deeksha Bhartiya, Mukesh Kumar Lalwani and 2 more (opens in a new tab)

PLoS ONE · 2013

doi:10.1371/journal.pone.0053823 (opens in a new tab)

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.

References 66

  1. 1.

    Li Y, Zheng H, Luo R, Wu H, Zhu H, et al (2011 ) Structural variation in two human genomes mapped at single-nucleotide resolution by whole genome de novo assembly. Nat Biotechnol 29: 723–730.

    Not in our library10.1038/nbt.1904 (opens in a new tab)

  2. 2.

    Hollox EJ (2012 ) The challenges of studying complex and dynamic regions of the human genome. Methods Mol Biol 838: 187–207.

    Not in our library10.1007/978-1-61779-507-7_9 (opens in a new tab)

  3. 3.

    Dinger ME, Amaral PP, Mercer TR, Mattick JS (2009 ) Pervasive transcription of the eukaryotic genome: functional indices and conceptual implications. Brief Funct Genomic Proteomic 8: 407–423.

    Not in our library10.1093/bfgp/elp038 (opens in a new tab)

  4. 4.

    Lander ES (2011 ) Initial impact of the sequencing of the human genome. Nature 470: 187–197.

    Not in our library10.1038/nature09792 (opens in a new tab)

  5. 5.

    Roberts A, Pimentel H, Trapnell C, Pachter L (2011 ) Identification of novel transcripts in annotated genomes using RNA-Seq. Bioinformatics 27: 2325–2329.

    Not in our library10.1093/bioinformatics/btr355 (opens in a new tab)

  6. 6.

    Severin AJ, Peiffer GA, Xu WW, Hyten DL, Bucciarelli B, et al (2010 ) An integrative approach to genomic introgression mapping. Plant Physiol 154: 3–12.

    Not in our library10.1104/pp.110.158949 (opens in a new tab)

  7. 7.

    1000 Genomes Project Consortium (2010 ) A map of human genome variation from population-scale sequencing. Nature 467: 1061–1073.

    Not in our library10.1038/nature09534 (opens in a new tab)

  8. 8.

    ENCODE Project Consortium (2004 ) The ENCODE (ENCyclopedia Of DNA Elements) Project. Science 306: 636–640.

    Not in our library10.1126/science.1105136 (opens in a new tab)

  9. 9.

    Wang Z, Gerstein M, Snyder M (2009 ) RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet 10: 57–63.

    Not in our library10.1038/nrg2484 (opens in a new tab)

  10. 10.

    Janga SC, Vallabhaneni S (2011 ) MicroRNAs as post-transcriptional machines and their interplay with cellular networks. Adv Exp Med Biol 722: 59–74.

    Not in our library10.1007/978-1-4614-0332-6_4 (opens in a new tab)

  11. 11.

    Zhao Y, He S, Liu C, Ru S, Zhao H, et al (2008 ) MicroRNA regulation of messenger-like noncoding RNAs: a network of mutual microRNA control. Trends Genet 24: 323–327.

    Not in our library10.1016/j.tig.2008.04.004 (opens in a new tab)

  12. 12.

    Zhang R, Su B (2009 ) Small but influential: the role of microRNAs on gene regulatory network and 3'UTR evolution. J Genet Genomics 36: 1–6.

    Not in our library10.1016/s1673-8527(09)60001-1 (opens in a new tab)

  13. 13.

    de Planell-Saguer M, Rodicio MC (2011 ) Analytical aspects of microRNA in diagnostics: a review. Anal Chim Acta 699: 134–152.

    Not in our library10.1016/j.aca.2011.05.025 (opens in a new tab)

  14. 14.

    Esteller M (2011 ) Non-coding RNAs in human disease. Nat Rev Genet 12: 861–874.

    Not in our library10.1038/nrg3074 (opens in a new tab)

  15. 15.

    Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R (2005 ) Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 123: 631–640.

    Not in our library10.1016/j.cell.2005.10.022 (opens in a new tab)

  16. 16.

    Iwasaki S, Tomari Y (2009 ) Argonaute-mediated translational repression (and activation). Fly (Austin ) 3: 204–206.

    Not in our library

  17. 17.

    Sayed D, Abdellatif M (2011 ) MicroRNAs in development and disease. Physiol Rev 91: 827–887.

    Not in our library10.1152/physrev.00006.2010 (opens in a new tab)

  18. 18.

    Wienholds E, Plasterk RH (2005 ) MicroRNA function in animal development. FEBS Lett 579: 5911–5922.

    Not in our library10.1016/j.febslet.2005.07.070 (opens in a new tab)

  19. 19.

    Fiore R, Khudayberdiev S, Saba R, Schratt G (2011 ) MicroRNA function in the nervous system. Prog Mol Biol Transl Sci 102: 47–100.

    Not in our library10.1016/b978-0-12-415795-8.00004-0 (opens in a new tab)

  20. 20.

    Fichtlscherer S, Zeiher AM, Dimmeler S (2011 ) Circulating microRNAs: biomarkers or mediators of cardiovascular diseases? Arterioscler Thromb Vasc Biol 31: 2383–2390.

    Not in our library10.1161/atvbaha.111.226696 (opens in a new tab)

  21. 21.

    Rederstorff M, Huttenhofer A (2010 ) Small non-coding RNAs in disease development and host-pathogen interactions. Curr Opin Mol Ther 12: 684–694.

    Not in our library

  22. 22.
    Host-virus interaction: a new role for microRNAs · 2006
    No notice
  23. 23.

    Scaria V, Jadhav V (2007 ) microRNAs in viral oncogenesis. Retrovirology 4: 82.

    Not in our library10.1186/1742-4690-4-82 (opens in a new tab)

  24. 24.

    Hung T, Chang HY (2010 ) Long noncoding RNA in genome regulation: prospects and mechanisms. RNA Biol 7: 582–585.

    Not in our library10.4161/rna.7.5.13216 (opens in a new tab)

  25. 25.

    Mercer TR, Dinger ME, Mattick JS (2009 ) Long non-coding RNAs: insights into functions. Nat Rev Genet 10: 155–159.

    Not in our library10.1038/nrg2521 (opens in a new tab)

  26. 26.

    Liao Q, Liu C, Yuan X, Kang S, Miao R, et al (2011 ) Large-scale prediction of long non-coding RNA functions in a coding-non-coding gene co-expression network. Nucleic Acids Res 39: 3864–3878.

    Not in our library10.1093/nar/gkq1348 (opens in a new tab)

  27. 27.

    Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, et al (2010 ) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464: 1071–1076.

    Not in our library10.1038/nature08975 (opens in a new tab)

  28. 28.

    Wan Y, Chang HY (2010 ) HOTAIR: Flight of noncoding RNAs in cancer metastasis. Cell Cycle 9: 3391–3392.

    Not in our library10.4161/cc.9.17.13122 (opens in a new tab)

  29. 29.

    Pontier DB, Gribnau J (2011 ) Xist regulation and function explored. Hum Genet 130: 223–236.

    Not in our library10.1007/s00439-011-1008-7 (opens in a new tab)

  30. 30.

    Xu C, Yang M, Tian J, Wang X, Li Z (2011 ) MALAT-1: a long non-coding RNA and its important 3' end functional motif in colorectal cancer metastasis. Int J Oncol 39: 169–175.

    Not in our library10.3892/ijo.2011.1007 (opens in a new tab)

  31. 31.

    Bhartiya D, Kapoor S, Jalali S, Sati S, Kaushik K, et al (2012 ) Conceptual approaches for lncRNA drug discovery and future strategies. Expert Opin Drug Discov 7: 503–513.

    Not in our library10.1517/17460441.2012.682055 (opens in a new tab)

  32. 32.

    Jalali S, Jayaraj GG, Scaria V (2012 ) Integrative transcriptome analysis suggest processing of a subset of long non-coding RNAs to small RNAs. Biol Direct 7: 25.

    Not in our library10.1186/1745-6150-7-25 (opens in a new tab)

  33. 33.

    Collins LJ (2011 ) The RNA infrastructure: an introduction to ncRNA networks. Adv Exp Med Biol 722: 1–19.

    Not in our library10.1007/978-1-4614-0332-6_1 (opens in a new tab)

  34. 34.

    Xu J, Li CX, Li YS, Lv JY, Ma Y, et al (2011 ) MiRNA-miRNA synergistic network: construction via co-regulating functional modules and disease miRNA topological features. Nucleic Acids Res 39: 825–836.

    Not in our library10.1093/nar/gkq832 (opens in a new tab)

  35. 35.

    Jeggari A, Marks DS, Larsson E (2012 ) miRcode: a map of putative microRNA target sites in the long non-coding transcriptome. Bioinformatics 28: 2062–2063.

    Not in our library10.1093/bioinformatics/bts344 (opens in a new tab)

  36. 36.

    Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP (2011 ) A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146: 353–358.

    Not in our library10.1016/j.cell.2011.07.014 (opens in a new tab)

  37. 37.

    Wang J, Liu X, Wu H, Ni P, Gu Z, et al (2010 ) CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res 38: 5366–5383.

    Not in our library10.1093/nar/gkq285 (opens in a new tab)

  38. 38.

    Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, et al (2011 ) A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147: 358–369.

    Not in our library10.1016/j.cell.2011.09.028 (opens in a new tab)

  39. 39.

    Franco-Zorrilla JM, Valli A, Todesco M, Mateos I, Puga MI, et al (2007 ) Target mimicry provides a new mechanism for regulation of microRNA activity. Nat Genet 39: 1033–1037.

    Not in our library10.1038/ng2079 (opens in a new tab)

  40. 40.
    A Collection of Target Mimics for Comprehensive Analysis of MicroRNA Function in Arabidopsis thaliana · 2010
    No notice
All 66 references

Cited by papers we hold 15

Questions about this paper

We email you if it is retracted, withdrawn, corrected or flagged.

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.