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The Scientific World Journal
Volume 2012, Article ID 541786, 11 pages
http://dx.doi.org/10.1100/2012/541786
Review Article

Molecular Mechanisms and Function Prediction of Long Noncoding RNA

Institute of Biostatistics, School of Life Science, Fudan University, 220 Handan Road, Shanghai 2004333, China

Received 30 October 2012; Accepted 21 November 2012

Academic Editors: G. P. Chrousos and T. Kino

Copyright © 2012 Handong Ma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P. Carninci, T. Kasukawa, S. Katayama et al., “The transcriptional landscape of the mammalian genome,” Science, vol. 309, pp. 1559–1563, 2005. View at Google Scholar
  2. E. Birney, J. A. Stamatoyannopoulos, A. Dutta et al., “Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project,” Nature, vol. 447, pp. 799–816, 2007. View at Publisher · View at Google Scholar
  3. P. Kapranov, J. Cheng, S. Dike et al., “RNA maps reveal new RNA classes and a possible function for pervasive transcription,” Science, vol. 316, no. 5830, pp. 1484–1488, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. J. E. Wilusz, S. M. Freier, and D. L. Spector, “3′ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA,” Cell, vol. 135, no. 5, pp. 919–932, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. A. C. Seila, J. M. Calabrese, S. S. Levine et al., “Divergent transcription from active promoters,” Science, vol. 322, no. 5909, pp. 1849–1851, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. J. L. Rinn, M. Kertesz, J. K. Wang et al., “Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs,” Cell, vol. 129, no. 7, pp. 1311–1323, 2007. View at Publisher · View at Google Scholar · View at Scopus
  7. H. Jia, M. Osak, G. K. Bogu, L. W. Stanton, R. Johnson, and L. Lipovich, “Genome-wide computational identification and manual annotation of human long noncoding RNA genes,” RNA, vol. 16, no. 8, pp. 1478–1487, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. U. A. Ørom, T. Derrien, M. Beringer et al., “Long noncoding RNAs with enhancer-like function in human cells,” Cell, vol. 143, no. 1, pp. 46–58, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. I. A. Qureshi, J. S. Mattick, and M. F. Mehler, “Long non-coding RNAs in nervous system function and disease,” Brain Research, vol. 1338, no. C, pp. 20–35, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. O. Wapinski and H. Y. Chang, “Long noncoding RNAs and human disease,” Trends in Cell Biology, vol. 21, no. 6, pp. 354–361, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. K. C. Wang and H. Y. Chang, “Molecular mechanisms of long noncoding RNAs,” Molecular Cell, vol. 43, pp. 904–914, 2011. View at Google Scholar
  12. T. Derrien, R. Johnson, G. Bussotti, A. Tanzer, S. Djebali et al., “The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression,” Genome Research, vol. 22, pp. 1775–1789, 2012. View at Google Scholar
  13. M. E. Dinger, K. C. Pang, T. R. Mercer, and J. S. Mattick, “Differentiating protein-coding and noncoding RNA: challenges and ambiguities,” PLoS Computational Biology, vol. 4, no. 11, Article ID e1000176, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. J. L. Rinn and H. Y. Chang, “Genome regulation by long noncoding RNAs,” Annual Review of Biochemistry, vol. 81, pp. 145–166, 2012. View at Google Scholar
  15. C. P. Ponting, P. L. Oliver, and W. Reik, “Evolution and functions of long noncoding RNAs,” Cell, vol. 136, no. 4, pp. 629–641, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. J.-W. Nam and D. P. Bartel, “Long noncoding RNAs in C. elegans,” Genome Research, vol. 22, no. 12, pp. 2529–2540, 2012. View at Publisher · View at Google Scholar
  17. M. C. Tsai, R. C. Spitale, and H. Y. Chang, “Long intergenic noncoding RNAs: new links in cancer progression,” Cancer Research, vol. 71, no. 1, pp. 3–7, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. J. Liu, J. Gough, and B. Rost, “Distinguishing protein-coding from non-coding RNAs through support vector machines,” PLoS genetics, vol. 2, no. 4, article no. e29, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. S. F. Altschul, T. L. Madden, A. A. Schäffer et al., “Gapped BLAST and PSI-BLAST: a new generation of protein database search programs,” Nucleic Acids Research, vol. 25, no. 17, pp. 3389–3402, 1997. View at Publisher · View at Google Scholar · View at Scopus
  20. L. Kong, Y. Zhang, Z. Q. Ye et al., “CPC: assess the protein-coding potential of transcripts using sequence features and support vector machine,” Nucleic Acids Research, vol. 35, pp. W345–W349, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. Z. J. Lu, K. Y. Yip, G. Wang et al., “Prediction and characterization of noncoding RNAs in C. elegans by integrating conservation, secondary structure, and high-throughput sequencing and array data,” Genome Research, vol. 21, no. 5, pp. 276–285, 2011. View at Google Scholar · View at Scopus
  22. R. R. Pandey, T. Mondal, F. Mohammad et al., “Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation,” Molecular Cell, vol. 32, no. 2, pp. 232–246, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. F. Mohammad, T. Mondal, and C. Kanduri, “Epigenetics of imprinted long noncoding RNAs,” Epigenetics, vol. 4, no. 5, pp. 277–286, 2009. View at Google Scholar · View at Scopus
  24. M. Huarte, M. Guttman, D. Feldser et al., “A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response,” Cell, vol. 142, no. 3, pp. 409–419, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. T. Hung, Y. Wang, M. F. Lin et al., “Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters,” Nature Genetics, vol. 43, no. 7, pp. 621–629, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. S. Loewer, M. N. Cabili, M. Guttman et al., “Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells,” Nature Genetics, vol. 42, no. 12, pp. 1113–1117, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. S. Swiezewski, F. Liu, A. Magusin, and C. Dean, “Cold-induced silencing by long antisense transcripts of an Arabidopsis Polycomb target,” Nature, vol. 462, no. 7274, pp. 799–802, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. J. B. Heo and S. Sung, “Vernalization-mediated epigenetic silencing by a long intronic noncoding RNA,” Science, vol. 331, no. 6013, pp. 76–79, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. T. K. Kim, M. Hemberg, J. M. Gray et al., “Widespread transcription at neuronal activity-regulated enhancers,” Nature, vol. 465, no. 7295, pp. 182–187, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. D. Wang, I. Garcia-Bassets, C. Benner et al., “Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA,” Nature, vol. 474, no. 7351, pp. 390–397, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Kino, D. E. Hurt, T. Ichijo, N. Nader, and G. P. Chrousos, “Noncoding RNA Gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor,” Science Signaling, vol. 3, no. 107, article no. ra8, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Gong and L. E. Maquat, “LncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 39 UTRs via Alu eleme,” Nature, vol. 470, no. 7333, pp. 284–288, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. I. Martianov, A. Ramadass, A. Serra Barros, N. Chow, and A. Akoulitchev, “Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript,” Nature, vol. 445, no. 7128, pp. 666–670, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. S. Redon, P. Reichenbach, and J. Lingner, “The non-coding RNA TERRA is a natural ligand and direct inhibitor of human telomerase,” Nucleic Acids Research, vol. 38, no. 17, Article ID gkq296, pp. 5797–5806, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. T. Hung and H. Y. Chang, “Long noncoding RNA in genome regulation: prospects and mechanisms,” RNA Biology, vol. 7, no. 5, pp. 582–585, 2010. View at Google Scholar · View at Scopus
  36. L. Poliseno, L. Salmena, J. Zhang, B. Carver, W. J. Haveman, and P. P. Pandolfi, “A coding-independent function of gene and pseudogene mRNAs regulates tumour biology,” Nature, vol. 465, no. 7301, pp. 1033–1038, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. M. S. Song, A. Carracedo, L. Salmena et al., “Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner,” Cell, vol. 144, no. 2, pp. 187–199, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. V. Tripathi, J. D. Ellis, Z. Shen et al., “The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation,” Molecular Cell, vol. 39, no. 6, pp. 925–938, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. D. Bernard, K. V. Prasanth, V. Tripathi et al., “A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression,” EMBO Journal, vol. 29, no. 18, pp. 3082–3093, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. K. Plath, S. Mlynarczyk-Evans, D. A. Nusinow, and B. Panning, “Xist RNA and the mechanism of X chromosome inactivation,” Annual Review of Genetics, vol. 36, pp. 233–278, 2002. View at Publisher · View at Google Scholar · View at Scopus
  41. J. T. Lee, “The X as model for RNA's niche in epigenomic regulation,” Cold Spring Harbor Perspectives in Biology, vol. 2, no. 9, Article ID a003749, 2010. View at Google Scholar · View at Scopus
  42. B. K. Sun, A. M. Deaton, and J. T. Lee, “A transient heterochromatic state in Xist preempts X inactivation choice without RNA stabilization,” Molecular Cell, vol. 21, no. 5, pp. 617–628, 2006. View at Publisher · View at Google Scholar · View at Scopus
  43. T. Nagano, J. A. Mitchell, L. A. Sanz et al., “The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin,” Science, vol. 322, no. 5908, pp. 1717–1720, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. J. Camblong, N. Iglesias, C. Fickentscher, G. Dieppois, and F. Stutz, “Antisense RNA stabilization induces transcriptional gene silencing via histone seacetylation in S. cerevisiae,” Cell, vol. 131, no. 4, pp. 706–717, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. K. C. Wang, Y. W. Yang, B. Liu et al., “A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression,” Nature, vol. 472, no. 7341, pp. 120–126, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. A. M. Khalil, M. Guttman, M. Huarte et al., “Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 28, pp. 11667–11672, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. J. Zhao, T. K. Ohsumi, J. T. Kung et al., “Genome-wide identification of polycomb-associated RNAs by RIP-seq,” Molecular Cell, vol. 40, no. 6, pp. 939–953, 2010. View at Publisher · View at Google Scholar · View at Scopus
  48. D. Tian, S. Sun, and J. T. Lee, “The long noncoding RNA, Jpx, Is a molecular switch for X chromosome inactivation,” Cell, vol. 143, no. 3, pp. 390–403, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. K. Collins, “Physiological assembly and activity of human telomerase complexes,” Mechanisms of Ageing and Development, vol. 129, no. 1-2, pp. 91–98, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. D. C. Zappulla and T. R. Cech, “Yeast telomerase RNA: a flexible scaffold for protein subunits,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 27, pp. 10024–10029, 2004. View at Publisher · View at Google Scholar · View at Scopus
  51. M. C. Tsai, O. Manor, Y. Wan et al., “Long noncoding RNA as modular scaffold of histone modification complexes,” Science, vol. 329, no. 5992, pp. 689–693, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. Y. Kotake, T. Nakagawa, K. Kitagawa et al., “Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15INK4B tumor suppressor gene,” Oncogene, vol. 30, no. 16, pp. 1956–1962, 2011. View at Publisher · View at Google Scholar · View at Scopus
  53. K. L. Yap, S. Li, A. M. Muñoz-Cabello et al., “Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a,” Molecular Cell, vol. 38, no. 5, pp. 662–674, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. C. Maison, D. Bailly, D. Roche et al., “SUMOylation promotes de novo targeting of HP1alpha to pericentric heterochromatin,” Nature Genetics, vol. 43, no. 3, pp. 220–227, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. P. P. Amaral, M. B. Clark, D. K. Gascoigne, M. E. Dinger, and J. S. Mattick, “LncRNAdb: a reference database for long noncoding RNAs,” Nucleic Acids Research, vol. 39, no. 1, pp. D146–D151, 2011. View at Publisher · View at Google Scholar · View at Scopus
  56. D. Bu, K. Yu, S. Sun, C. Xie, G. Skogerbo et al., “NONCODE v3. 0: integrative annotation of long noncoding RNAs,” Nucleic Acids Research, vol. 40, pp. D210–D215, 2012. View at Google Scholar
  57. P. J. Volders, K. Helsens, X. Wang, B. Menten, L. Martens et al., “LNCipedia: a database for annotated human lncRNA transcript sequences and structures,” Nucleic Acids Research. In press. View at Publisher · View at Google Scholar
  58. T. Kin, K. Yamada, G. Terai et al., “fRNAdb: a platform for mining/annotating functional RNA candidates from non-coding RNA sequences,” Nucleic Acids Research, vol. 35, no. 1, pp. D145–D148, 2007. View at Publisher · View at Google Scholar · View at Scopus
  59. M. E. Dinger, K. C. Pang, T. R. Mercer, M. L. Crowe, S. M. Grimmond, and J. S. Mattick, “NRED: a database of long noncoding RNA expression,” Nucleic Acids Research, vol. 37, no. 1, pp. D122–D126, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. S. K. Michelhaugh, L. Lipovich, J. Blythe, H. Jia, G. Kapatos, and M. J. Bannon, “Mining Affymetrix microarray data for long non-coding RNAs: altered expression in the nucleus accumbens of heroin abusers,” Journal of Neurochemistry, vol. 116, no. 3, pp. 459–466, 2011. View at Publisher · View at Google Scholar · View at Scopus
  61. T. Babak, B. J. Blencowe, and T. R. Hughes, “A systematic search for new mammalian noncoding RNAs indicates little conserved intergenic transcription,” BMC Genomics, vol. 6, article no. 14, 2005. View at Publisher · View at Google Scholar · View at Scopus
  62. E. A. Gibb, E. A. Vucic, K. S. Enfield, G. L. Stewart, K. M. Lonergan et al., “Human cancer long non-coding RNA transcriptomes,” PLoS One, vol. 6, Article ID e25915, 2011. View at Publisher · View at Google Scholar
  63. T. L. Lee, A. Xiao, and O. M. Rennert, “Identification of novel long noncoding RNA transcripts in male germ cells,” Methods in Molecular Biology, vol. 825, pp. 105–114, 2012. View at Google Scholar
  64. M. Furuno, K. C. Pang, N. Ninomiya et al., “Clusters of internally primed transcripts reveal novel long noncoding RNAs,” PLoS Genetics, vol. 2, no. 4, article no. e37, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. W. Huang, N. Long, and H. Khatib, “Genome-wide identification and initial characterization of bovine long non-coding RNAs from EST data,” Animal Genetics, vol. 43, pp. 674–682, 2012. View at Google Scholar
  66. T. Li, S. Wang, R. Wu, X. Zhou, D. Zhu et al., “Identification of long non-protein coding RNAs in chicken skeletal muscle using next generation sequencing,” Genomics, vol. 99, pp. 292–298, 2012. View at Google Scholar
  67. A. Pauli, E. Valen, M. F. Lin, M. Garber, N. L. Vastenhouw et al., “Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis,” Genome Research, vol. 22, pp. 577–591, 2012. View at Google Scholar
  68. J. R. Prensner, M. K. Iyer, O. A. Balbin et al., “Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression,” Nature Biotechnology, vol. 29, no. 8, pp. 742–749, 2011. View at Publisher · View at Google Scholar · View at Scopus
  69. J. Zhao, B. K. Sun, J. A. Erwin, J. J. Song, and J. T. Lee, “Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome,” Science, vol. 322, no. 5902, pp. 750–756, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. P. J. Park, “ChIP-seq: advantages and challenges of a maturing technology,” Nature Reviews Genetics, vol. 10, no. 10, pp. 669–680, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. M. Guttman, I. Amit, M. Garber et al., “Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals,” Nature, vol. 458, no. 7235, pp. 223–227, 2009. View at Publisher · View at Google Scholar · View at Scopus
  72. Y. Okazaki, M. Furuno, T. Kasukawa et al., “Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs,” Nature, vol. 420, no. 6915, pp. 563–573, 2002. View at Publisher · View at Google Scholar · View at Scopus
  73. X. Yang, T. J. Tschaplinski, G. B. Hurst et al., “Discovery and annotation of small proteins using genomics, proteomics, and computational approaches,” Genome Research, vol. 21, no. 4, pp. 634–641, 2011. View at Publisher · View at Google Scholar · View at Scopus
  74. M. F. Lin, J. W. Carlson, M. A. Crosby et al., “Revisiting the protein-coding gene catalog of Drosophila melanogaster using 12 fly genomes,” Genome Research, vol. 17, no. 12, pp. 1823–1836, 2007. View at Publisher · View at Google Scholar · View at Scopus
  75. M. Clamp, B. Fry, M. Kamal et al., “Distinguishing protein-coding and noncoding genes in the human genome,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 49, pp. 19428–19433, 2007. View at Publisher · View at Google Scholar · View at Scopus
  76. M. F. Lin, I. Jungreis, and M. Kellis, “PhyloCSF: a comparative genomics method to distinguish protein coding and non-coding regions,” Bioinformatics, vol. 27, no. 13, Article ID btr209, pp. i275–i282, 2011. View at Publisher · View at Google Scholar · View at Scopus
  77. S. Washietl, S. Findeiß, S. A. Müller et al., “RNAcode: robust discrimination of coding and noncoding regions in comparative sequence data,” RNA, vol. 17, no. 4, pp. 578–594, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. E. Rivas and S. R. Eddy, “Noncoding RNA gene detection using comparative sequence analysis,” BMC Bioinformatics, vol. 2, article no. 8, 2001. View at Publisher · View at Google Scholar · View at Scopus
  79. S. Washietl, I. L. Hofacker, and P. F. Stadler, “Fast and reliable prediction of noncoding RNAs,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 7, pp. 2454–2459, 2005. View at Publisher · View at Google Scholar · View at Scopus
  80. J. S. Pedersen, G. Bejerano, A. Siepel et al., “Identification and classification of conserved RNA secondary structures in the human genome,” PLoS Computational Biology, vol. 2, no. 4, article no. e33, pp. 251–262, 2006. View at Publisher · View at Google Scholar · View at Scopus
  81. L. Duret, C. Chureau, S. Samain, J. Weissanbach, and P. Avner, “The Xist RNA gene evolved in eutherians by pseudogenization of a protein-coding gene,” Science, vol. 312, no. 5780, pp. 1653–1655, 2006. View at Publisher · View at Google Scholar · View at Scopus
  82. S. Chooniedass-Kothari, E. Emberley, M. K. Hamedani et al., “The steroid receptor RNA activator is the first functional RNA encoding a protein,” FEBS Letters, vol. 566, no. 1-3, pp. 43–47, 2004. View at Publisher · View at Google Scholar · View at Scopus
  83. E. D. Kim and S. Sung, “Long noncoding RNA: unveiling hidden layer of gene regulatory networks,” Trends in Plant Science, vol. 17, pp. 16–21, 2012. View at Google Scholar
  84. M. Hiller, S. Findeiß, S. Lein et al., “Conserved introns reveal novel transcripts in Drosophila melanogaster,” Genome Research, vol. 19, no. 7, pp. 1289–1300, 2009. View at Publisher · View at Google Scholar · View at Scopus
  85. J. S. Mattick, “The genetic signatures of noncoding RNAs,” PLoS Genetics, vol. 5, no. 4, Article ID e1000459, 2009. View at Publisher · View at Google Scholar · View at Scopus
  86. E. Bernstein and C. D. Allis, “RNA meets chromatin,” Genes and Development, vol. 19, no. 14, pp. 1635–1655, 2005. View at Publisher · View at Google Scholar · View at Scopus
  87. J. Whitehead, G. K. Pandey, and C. Kanduri, “Regulation of the mammalian epigenome by long noncoding RNAs,” Biochimica et Biophysica Acta, vol. 1790, no. 9, pp. 936–947, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. J. E. Wilusz, H. Sunwoo, and D. L. Spector, “Long noncoding RNAs: functional surprises from the RNA world,” Genes and Development, vol. 23, no. 13, pp. 1494–1504, 2009. View at Publisher · View at Google Scholar · View at Scopus
  89. M. Beltran, I. Puig, C. Peña et al., “A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition,” Genes and Development, vol. 22, no. 6, pp. 756–769, 2008. View at Publisher · View at Google Scholar · View at Scopus
  90. U. A. Ørom and R. Shiekhattar, “Noncoding RNAs and enhancers: complications of a long-distance relationship,” Trends in Genetics, vol. 27, pp. 433–439, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. J. S. Mattick and I. V. Makunin, “Small regulatory RNAs in mammals,” Human Molecular Genetics, vol. 14, no. 1, pp. R121–R132, 2005. View at Publisher · View at Google Scholar · View at Scopus
  92. T. Nagano and P. Fraser, “No-nonsense functions for long noncoding RNAs,” Cell, vol. 145, no. 2, pp. 178–181, 2011. View at Publisher · View at Google Scholar · View at Scopus
  93. M. Guttman, J. Donaghey, B. W. Carey, M. Garber, J. K. Grenier et al., “lincRNAs act in the circuitry controlling pluripotency and differentiation,” Nature, vol. 477, pp. 295–300, 2011. View at Google Scholar
  94. R. Johnson, “Long non-coding RNAs in Huntington's disease neurodegeneration,” Neurobiology of Disease, vol. 46, pp. 245–254, 2012. View at Google Scholar
  95. F. De Santa, I. Barozzi, F. Mietton et al., “A large fraction of extragenic RNA Pol II transcription sites overlap enhancers,” PLoS Biology, vol. 8, no. 5, Article ID e1000384, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. Z. H. Li and T. M. Rana, “Molecular mechanisms of RNA-triggered gene silencing machineries,” Accounts of Chemical Research, vol. 45, pp. 1122–1131, 2012. View at Google Scholar
  97. J. Ponjavic, P. L. Oliver, G. Lunter, and C. P. Ponting, “Genomic and transcriptional co-localization of protein-coding and long non-coding RNA pairs in the developing brain,” PLoS Genetics, vol. 5, no. 8, Article ID e1000617, 2009. View at Publisher · View at Google Scholar · View at Scopus
  98. M. Ebisuya, T. Yamamoto, M. Nakajima, and E. Nishida, “Ripples from neighbouring transcription,” Nature Cell Biology, vol. 10, no. 9, pp. 1106–1113, 2008. View at Publisher · View at Google Scholar · View at Scopus
  99. C. J. Brown, A. Ballabio, J. L. Rupert et al., “A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome,” Nature, vol. 349, no. 6304, pp. 38–44, 1991. View at Publisher · View at Google Scholar · View at Scopus
  100. F. Sleutels, R. Zwart, and D. P. Barlow, “The non-coding Air RNA is required for silencing autosomal imprinted genes,” Nature, vol. 415, no. 6873, pp. 810–813, 2002. View at Google Scholar · View at Scopus
  101. J. T. Lee, “Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome,” Genes and Development, vol. 23, no. 16, pp. 1831–1842, 2009. View at Publisher · View at Google Scholar · View at Scopus
  102. K. M. Schmitz, C. Mayer, A. Postepska, and I. Grummt, “Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes,” Genes and Development, vol. 24, no. 20, pp. 2264–2269, 2010. View at Publisher · View at Google Scholar · View at Scopus
  103. A. T. Willingham, A. P. Orth, S. Batalov et al., “Molecular biology: a strategy for probing the function of noncoding RNAs finds a repressor of NFAT,” Science, vol. 309, no. 5740, pp. 1570–1573, 2005. View at Publisher · View at Google Scholar · View at Scopus
  104. T. R. Mercer, M. E. Dinger, and J. S. Mattick, “Long non-coding RNAs: insights into functions,” Nature Reviews Genetics, vol. 10, no. 3, pp. 155–159, 2009. View at Publisher · View at Google Scholar · View at Scopus
  105. K. C. Pang, M. E. Dinger, T. R. Mercer et al., “Genome-wide identification of long noncoding RNAs in CD8+ T cells,” Journal of Immunology, vol. 182, no. 12, pp. 7738–7748, 2009. View at Publisher · View at Google Scholar · View at Scopus
  106. A. N. Khachane and P. M. Harrison, “Mining mammalian transcript data for functional long non-coding RNAs,” PLoS One, vol. 5, no. 4, Article ID e10316, 2010. View at Publisher · View at Google Scholar · View at Scopus
  107. Q. Liao, C. Liu, X. Yuan et al., “Large-scale prediction of long non-coding RNA functions in a coding-non-coding gene co-expression network,” Nucleic Acids Research, vol. 39, no. 9, pp. 3864–3878, 2011. View at Publisher · View at Google Scholar · View at Scopus
  108. C. Braconi, T. Kogure, N. Valeri et al., “microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer,” Oncogene, vol. 30, pp. 4750–4756, 2011. View at Publisher · View at Google Scholar · View at Scopus
  109. M. S. Ebert and P. A. Sharp, “Emerging roles for natural microRNA sponges,” Current Biology, vol. 20, no. 19, pp. R858–R861, 2010. View at Publisher · View at Google Scholar · View at Scopus
  110. A. Jeggari, D. S. Marks, and E. Larsson, “miRcode: a map of putative microRNA target sites in the long non-coding transcriptome,” Bioinformatics, vol. 28, pp. 2062–2063, 2012. View at Google Scholar
  111. M. Bellucci, F. Agostini, M. Masin, and G. G. Tartaglia, “Predicting protein associations with long noncoding RNAs,” Nature Methods, vol. 8, no. 6, pp. 444–445, 2011. View at Publisher · View at Google Scholar · View at Scopus