Skip to main content

Advertisement

Log in

Long non-coding RNA in health and disease

  • Review
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Long non-coding RNAs (lncRNAs) interact with the nuclear architecture and are involved in fundamental biological mechanisms, such as imprinting, histone-code regulation, gene activation, gene repression, lineage determination, and cell proliferation, all by regulating gene expression. Understanding the lncRNA regulation of transcriptional or post-transcriptional gene regulation expands our knowledge of disease. Several associations between altered lncRNA function and gene expression have been linked to clinical disease phenotypes. Early advances have been made in developing lncRNAs as biomarkers. Several mouse models reveal that human lncRNAs have very diverse functions. Their involvement in gene and genome regulation as well as disease underscores the importance of lncRNA-mediated regulatory networks. Because of their tissue-specific expression potential, their function as activators or repressors, and their selective targeting of genes, lncRNAs are of potential therapeutic interest. We review the regulatory mechanisms of lncRNAs, their major functional principles, and discuss their role in Mendelian disorders, cancer, cardiovascular disease, and neurological disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Notes

  1. Chromatin looping: Studying the structural properties and spatial organization of chromosomes is important for the understanding and evaluation of the regulation of gene expression, DNA replication and repair, and recombination. One example of chromosomal interaction is chromosome looping in which a chromosomal region can fold in order to bring an enhancer and associated TF within close proximity to a gene.

  2. PIWI: The piwi or PIWI, originally P-element-induced wimpy testis in Drosophila, class of genes was originally identified as encoding regulatory proteins responsible for maintaining incomplete differentiation in stem cells. PIWI proteins are highly conserved nucleic acid-binding proteins.

  3. CTCF: Transcriptional repressor CTCF, also known as 11-zinc finger protein or CCCTC-binding factor, is a transcription factor that is involved in many cellular processes, including transcriptional regulation, insulator activity, and regulation of chromatin architecture.

  4. Paraspeckle: A paraspeckle is an irregularly shaped cell compartment, approximately 0.2–1 μm in size, found in the nuclear interchromatin space.

References

  1. Waddington CH (2012) The epigenotype. 1942. Int J Epidemiol 41:10–13

    PubMed  CAS  Google Scholar 

  2. Mercer TR, Mattick JS (2013) Understanding the regulatory and transcriptional complexity of the genome through structure. Genome Res 23:1081–1088

    PubMed Central  PubMed  CAS  Google Scholar 

  3. Chen K, Rajewsky N (2007) The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet 8:93–103

    PubMed  CAS  Google Scholar 

  4. Poulos MG, Batra R, Charizanis K, Swanson MS (2011) Developments in RNA splicing and disease. Cold Spring Harb Perspect Biol 3:a000778

    PubMed Central  PubMed  Google Scholar 

  5. Phillips-Cremins JE, Corces VG (2013) Chromatin insulators: linking genome organization to cellular function. Mol Cell 50:461–474

    PubMed  CAS  Google Scholar 

  6. Odom DT et al (2007) Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat Genet 39:730–732

    PubMed Central  PubMed  CAS  Google Scholar 

  7. Vavouri T, Walter K, Gilks WR, Lehner B, Elgar G (2007) Parallel evolution of conserved non-coding elements that target a common set of developmental regulatory genes from worms to humans. Genome Biol 8:R15

    PubMed Central  PubMed  Google Scholar 

  8. Vavouri T, McEwen GK, Woolfe A, Gilks WR, Elgar G (2006) Defining a genomic radius for long-range enhancer action: duplicated conserved non-coding elements hold the key. Trends Genet 22:5–10

    PubMed  CAS  Google Scholar 

  9. Schubeler D, Francastel C, Cimbora DM, Reik A, Martin DI, Groudine M (2000) Nuclear localization and histone acetylation: a pathway for chromatin opening and transcriptional activation of the human beta-globin locus. Genes Dev 14:940–950

    PubMed Central  PubMed  CAS  Google Scholar 

  10. Vignali M, Hassan AH, Neely KE, Workman JL (2000) ATP-dependent chromatin-remodeling complexes. Mol Cell Biol 20:1899–1910

    PubMed Central  PubMed  CAS  Google Scholar 

  11. Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705

    PubMed  CAS  Google Scholar 

  12. Blackwood EM, Kadonaga JT (1998) Going the distance: a current view of enhancer action. Science 281:60–63

    PubMed  CAS  Google Scholar 

  13. Lee JT, Bartolomei MS (2013) X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell 152:1308–1323

    PubMed  CAS  Google Scholar 

  14. Berger SL (2002) Histone modifications in transcriptional regulation. Curr Opin Genet Dev 12:142–148

    PubMed  CAS  Google Scholar 

  15. Lee JS, Smith E, Shilatifard A (2010) The language of histone crosstalk. Cell 142:682–685

    PubMed Central  PubMed  CAS  Google Scholar 

  16. Kleinjan DA, van Heyningen V (2005) Long-range control of gene expression: emerging mechanisms and disruption in disease. Am J Hum Genet 76:8–32

    PubMed Central  PubMed  CAS  Google Scholar 

  17. Wijchers PJ, de Laat W (2011) Genome organization influences partner selection for chromosomal rearrangements. Trends Genet 27:63–71

    PubMed  CAS  Google Scholar 

  18. Maher B (2012) ENCODE: the human encyclopaedia. Nature 489:46–48

    PubMed  Google Scholar 

  19. Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, Rinn JL (2011) Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev 25:1915–1927

    PubMed Central  PubMed  CAS  Google Scholar 

  20. Guttman M et al (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223–227

    PubMed Central  PubMed  CAS  Google Scholar 

  21. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384–388

    PubMed  CAS  Google Scholar 

  22. Memczak S et al (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495:333–338

    PubMed  CAS  Google Scholar 

  23. Khalil AM et al (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A 106:11667–11672

    PubMed Central  PubMed  CAS  Google Scholar 

  24. Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145–166

    PubMed  CAS  Google Scholar 

  25. Kogo R et al (2011) Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res 71:6320–6326

    PubMed  CAS  Google Scholar 

  26. Brown CJ, Ballabio A, Rupert JL, Lafreniere RG, Grompe M, Tonlorenzi R, Willard HF (1991) A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349:38–44

    PubMed  CAS  Google Scholar 

  27. Dinger ME et al (2008) Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Res 18:1433–1445

    PubMed Central  PubMed  CAS  Google Scholar 

  28. Pauli A, Rinn JL, Schier AF (2011) Non-coding RNAs as regulators of embryogenesis. Nat Rev Genet 12:136–149

    PubMed  CAS  Google Scholar 

  29. Engreitz JM et al (2013) The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science 341:1237973

    PubMed Central  PubMed  Google Scholar 

  30. Simon MD et al (2013) High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation. Nature 504:465–469

    PubMed  CAS  Google Scholar 

  31. Lee JT, Davidow LS, Warshawsky D (1999) Tsix, a gene antisense to Xist at the X-inactivation centre. Nat Genet 21:400–404

    PubMed  CAS  Google Scholar 

  32. Tian D, Sun S, Lee JT (2010) The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell 143:390–403

    PubMed Central  PubMed  CAS  Google Scholar 

  33. Sun S, Del Rosario BC, Szanto A, Ogawa Y, Jeon Y, Lee JT (2013) Jpx RNA activates Xist by evicting CTCF. Cell 153:1537–1551

    PubMed Central  PubMed  CAS  Google Scholar 

  34. Rinn JL et al (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129:1311–1323

    PubMed Central  PubMed  CAS  Google Scholar 

  35. Nagano T, Mitchell JA, Sanz LA, Pauler FM, Ferguson-Smith AC, Feil R, Fraser P (2008) The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science 322:1717–1720

    PubMed  CAS  Google Scholar 

  36. Pandey RR, Mondal T, Mohammad F, Enroth S, Redrup L, Komorowski J, Nagano T, Mancini-Dinardo D, Kanduri C (2008) Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell 32:232–246

    PubMed  CAS  Google Scholar 

  37. Orom UA et al (2010) Long noncoding RNAs with enhancer-like function in human cells. Cell 143:46–58

    PubMed  CAS  Google Scholar 

  38. Wang KC et al (2011) A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472:120–124

    PubMed Central  PubMed  CAS  Google Scholar 

  39. Maass PG et al (2012) A misplaced lncRNA causes brachydactyly in humans. J Clin Invest 122:3990–4002

    PubMed Central  PubMed  CAS  Google Scholar 

  40. Strickfaden H, Zunhammer A, van Koningsbruggen S, Kohler D, Cremer T (2010) 4D chromatin dynamics in cycling cells: Theodor Boveri’s hypotheses revisited. Nucleus 1:284–297

    PubMed Central  PubMed  Google Scholar 

  41. Cremer T, Cremer M (2010) Chromosome territories. Cold Spring Harb Perspect Biol 2:a003889

    PubMed Central  PubMed  Google Scholar 

  42. Bickmore WA (2013) The spatial organization of the human genome. Annu Rev Genomics Hum Genet 14:67–84

    PubMed  CAS  Google Scholar 

  43. Fullwood MJ et al (2009) An oestrogen-receptor-alpha-bound human chromatin interactome. Nature 462:58–64

    PubMed Central  PubMed  CAS  Google Scholar 

  44. Lieberman-Aiden E et al (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289–293

    PubMed Central  PubMed  CAS  Google Scholar 

  45. Batista PJ, Chang HY (2013) Long noncoding RNAs: cellular address codes in development and disease. Cell 152:1298–1307

    PubMed Central  PubMed  CAS  Google Scholar 

  46. Hung T et al (2011) Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet 43:621–629

    PubMed Central  PubMed  CAS  Google Scholar 

  47. Zappulla DC, Cech TR (2006) RNA as a flexible scaffold for proteins: yeast telomerase and beyond. Cold Spring Harb Symp Quant Biol 71:217–224

    PubMed  CAS  Google Scholar 

  48. Mayer C, Schmitz KM, Li J, Grummt I, Santoro R (2006) Intergenic transcripts regulate the epigenetic state of rRNA genes. Mol Cell 22:351–361

    PubMed  CAS  Google Scholar 

  49. Schmitz KM, Mayer C, Postepska A, Grummt I (2010) Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes. Genes Dev 24:2264–2269

    PubMed Central  PubMed  CAS  Google Scholar 

  50. Huarte M et al (2010) A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142:409–419

    PubMed Central  PubMed  CAS  Google Scholar 

  51. Yoon JH et al (2012) LincRNA-p21 suppresses target mRNA translation. Mol Cell 47:648–655

    PubMed Central  PubMed  CAS  Google Scholar 

  52. Jeon Y, Lee JT (2011) YY1 tethers Xist RNA to the inactive X nucleation center. Cell 146:119–133

    PubMed Central  PubMed  CAS  Google Scholar 

  53. Gong C, Maquat LE (2011) lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements. Nature 470:284–288

    PubMed Central  PubMed  CAS  Google Scholar 

  54. Kretz M et al (2013) Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature 493:231–235

    PubMed Central  PubMed  CAS  Google Scholar 

  55. Klattenhoff CA et al (2013) Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell 152:570–583

    PubMed Central  PubMed  CAS  Google Scholar 

  56. Wagner LA, Christensen CJ, Dunn DM, Spangrude GJ, Georgelas A, Kelley L, Esplin MS, Weiss RB, Gleich GJ (2007) EGO, a novel, noncoding RNA gene, regulates eosinophil granule protein transcript expression. Blood 109:5191–5198

    PubMed Central  PubMed  CAS  Google Scholar 

  57. Grote P et al (2013) The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev Cell 24:206–214

    PubMed  CAS  Google Scholar 

  58. Barry G et al (2013) The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing. Mol Psychiatry. doi:10.1038/mp.2013.45

    PubMed  Google Scholar 

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

    PubMed Central  PubMed  CAS  Google Scholar 

  60. Khalil AM, Faghihi MA, Modarresi F, Brothers SP, Wahlestedt C (2008) A novel RNA transcript with antiapoptotic function is silenced in fragile X syndrome. PLoS ONE 3:e1486

    PubMed Central  PubMed  Google Scholar 

  61. Landers M, Calciano MA, Colosi D, Glatt-Deeley H, Wagstaff J, Lalande M (2005) Maternal disruption of Ube3a leads to increased expression of Ube3a-ATS in trans. Nucleic Acids Res 33:3976–3984

    PubMed Central  PubMed  CAS  Google Scholar 

  62. Meng L, Person RE, Beaudet AL (2012) Ube3a-ATS is an atypical RNA polymerase II transcript that represses the paternal expression of Ube3a. Hum Mol Genet 21:3001–3012

    PubMed Central  PubMed  CAS  Google Scholar 

  63. Yildirim E, Kirby JE, Brown DE, Mercier FE, Sadreyev RI, Scadden DT, Lee JT (2013) Xist RNA is a potent suppressor of hematologic cancer in mice. Cell 152:727–742

    PubMed  CAS  Google Scholar 

  64. Tripathi V et al (2010) The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell 39:925–938

    PubMed  CAS  Google Scholar 

  65. Schmidt LH et al (2011) The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. J Thorac Oncol 6:1984–1992

    PubMed  Google Scholar 

  66. Tripathi V et al (2013) Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet 9:e1003368

    PubMed Central  PubMed  CAS  Google Scholar 

  67. Wilusz JE, JnBaptiste CK, Lu LY, Kuhn CD, Joshua-Tor L, Sharp PA (2012) A triple helix stabilizes the 3′ ends of long noncoding RNAs that lack poly(A) tails. Genes Dev 26:2392–2407

    PubMed Central  PubMed  CAS  Google Scholar 

  68. Gupta RA et al (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464:1071–1076

    PubMed Central  PubMed  CAS  Google Scholar 

  69. Quagliata L et al (2013) lncRNA HOTTIP/HOXA13 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients. Hepatology. doi:10.1002/hep.26740

  70. Panzitt K et al (2007) Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology 132:330–342

    PubMed  CAS  Google Scholar 

  71. Wang J, Liu X, Wu H, Ni P, Gu Z, Qiao Y, Chen N, Sun F, Fan Q (2010) CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res 38:5366–5383

    PubMed Central  PubMed  CAS  Google Scholar 

  72. Du Y, Kong G, You X, Zhang S, Zhang T, Gao Y, Ye L, Zhang X (2012) Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18. J Biol Chem 287:26302–26311

    PubMed Central  PubMed  CAS  Google Scholar 

  73. Faghihi MA et al (2008) Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nat Med 14:723–730

    PubMed Central  PubMed  CAS  Google Scholar 

  74. Burd CE, Jeck WR, Liu Y, Sanoff HK, Wang Z, Sharpless NE (2010) Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet 6:e1001233

    PubMed Central  PubMed  Google Scholar 

  75. Pasmant E, Laurendeau I, Heron D, Vidaud M, Vidaud D, Bieche I (2007) Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF. Cancer Res 67:3963–3969

    PubMed  CAS  Google Scholar 

  76. Ge X, Chen Y, Liao X, Liu D, Li F, Ruan H, Jia W (2013) Overexpression of long noncoding RNA PCAT-1 is a novel biomarker of poor prognosis in patients with colorectal cancer. Med Oncol 30:588

    PubMed  Google Scholar 

  77. Prensner JR et al (2011) Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat Biotechnol 29:742–749

    PubMed Central  PubMed  CAS  Google Scholar 

  78. Prensner JR et al (2013) The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nat Genet 45:1392–1398

    PubMed  CAS  Google Scholar 

  79. Takayama K et al (2013) Androgen-responsive long noncoding RNA CTBP1-AS promotes prostate cancer. Embo J 32:1665–1680

    PubMed  CAS  Google Scholar 

  80. Lu P, Roberts CW (2013) The SWI/SNF tumor suppressor complex: regulation of promoter nucleosomes and beyond. Nucleus 4:374–378

    PubMed  Google Scholar 

  81. Wahlestedt C (2013) Targeting long non-coding RNA to therapeutically upregulate gene expression. Nat Rev Drug Discov 12:433–446

    PubMed  CAS  Google Scholar 

  82. Wheeler TM, Leger AJ, Pandey SK, MacLeod AR, Nakamori M, Cheng SH, Wentworth BM, Bennett CF, Thornton CA (2012) Targeting nuclear RNA for in vivo correction of myotonic dystrophy. Nature 488:111–115

    PubMed  CAS  Google Scholar 

  83. Eissmann M et al (2012) Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and development. RNA Biol 9:1076–1087

    PubMed Central  PubMed  CAS  Google Scholar 

  84. Zhang B et al (2012) The lncRNA Malat1 is dispensable for mouse development but its transcription plays a cis-regulatory role in the adult. Cell Rep 2:111–123

    PubMed Central  PubMed  CAS  Google Scholar 

  85. Nakagawa S, Naganuma T, Shioi G, Hirose T (2011) Paraspeckles are subpopulation-specific nuclear bodies that are not essential in mice. J Cell Biol 193:31–39

    PubMed Central  PubMed  CAS  Google Scholar 

  86. Nakagawa S, Ip JY, Shioi G, Tripathi V, Zong X, Hirose T, Prasanth KV (2012) Malat1 is not an essential component of nuclear speckles in mice. RNA 18:1487–1499

    PubMed Central  PubMed  CAS  Google Scholar 

  87. Li L et al (2013) Targeted disruption of Hotair leads to homeotic transformation and gene derepression. Cell Rep 5:3–12

    PubMed  CAS  Google Scholar 

  88. Sauvageau M et al (2013) Multiple knockout mouse models reveal lincRNAs are required for life and brain development. Elife 2:e01749

    PubMed Central  PubMed  Google Scholar 

  89. Zhang X et al (2009) A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster. Blood 113:2526–2534

    PubMed Central  PubMed  CAS  Google Scholar 

  90. Hu W, Yuan B, Flygare J, Lodish HF (2011) Long noncoding RNA-mediated anti-apoptotic activity in murine erythroid terminal differentiation. Genes Dev 25:2573–2578

    PubMed Central  PubMed  CAS  Google Scholar 

  91. Onoguchi M, Hirabayashi Y, Koseki H, Gotoh Y (2012) A noncoding RNA regulates the neurogenin1 gene locus during mouse neocortical development. Proc Natl Acad Sci U S A 109:16939–16944

    PubMed Central  PubMed  CAS  Google Scholar 

  92. Navarro P et al (2010) Molecular coupling of Tsix regulation and pluripotency. Nature 468:457–460

    PubMed  CAS  Google Scholar 

  93. Ogawa Y, Lee JT (2003) Xite, X-inactivation intergenic transcription elements that regulate the probability of choice. Mol Cell 11:731–743

    PubMed  CAS  Google Scholar 

  94. van Dijk M et al (2012) HELLP babies link a novel lincRNA to the trophoblast cell cycle. J Clin Invest 122:4003–4011

    PubMed Central  PubMed  Google Scholar 

  95. Sonkoly E et al (2005) Identification and characterization of a novel, psoriasis susceptibility-related noncoding RNA gene, PRINS. J Biol Chem 280:24159–24167

    PubMed  CAS  Google Scholar 

  96. Beckedorff FC, Ayupe AC, Crocci-Souza R, Amaral MS, Nakaya HI, Soltys DT, Menck CF, Reis EM, Verjovski-Almeida S (2013) The intronic long noncoding RNA ANRASSF1 recruits PRC2 to the RASSF1A promoter, reducing the expression of RASSF1A and increasing cell proliferation. PLoS Genet 9:e1003705

    PubMed Central  PubMed  CAS  Google Scholar 

  97. Cunnington MS, Santibanez Koref M, Mayosi BM, Burn J, Keavney B (2010) Chromosome 9p21 SNPs associated with multiple disease phenotypes correlate with anril expression. PLoS Genet 6:e1000899

    PubMed Central  PubMed  Google Scholar 

  98. Kotake Y, Nakagawa T, Kitagawa K, Suzuki S, Liu N, Kitagawa M, Xiong Y (2011) Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene 30:1956–1962

    PubMed Central  PubMed  CAS  Google Scholar 

  99. Pasmant E, Sabbagh A, Vidaud M, Bieche I (2011) ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J 25:444–448

    PubMed  CAS  Google Scholar 

  100. Yap KL, Li S, Munoz-Cabello AM, Raguz S, Zeng L, Mujtaba S, Gil J, Walsh MJ, Zhou MM (2010) Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell 38:662–674

    PubMed Central  PubMed  CAS  Google Scholar 

  101. Arita T et al (2013) Circulating long non-coding RNAs in plasma of patients with gastric cancer. Anticancer Res 33:3185–3193

    PubMed  CAS  Google Scholar 

  102. Kallen AN et al (2013) The imprinted H19 lncRNA antagonizes let-7 microRNAs. Mol Cell 52:101–112

    PubMed  CAS  Google Scholar 

  103. Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-lail R, Hochberg A, Galun E (2007) The H19 non-coding RNA is essential for human tumor growth. PLoS ONE 2:e845

    PubMed Central  PubMed  Google Scholar 

  104. Thorvaldsen JL, Duran KL, Bartolomei MS (1998) Deletion of the H19 differentially methylated domain results in loss of imprinted expression of H19 and Igf2. Genes Dev 12:3693–3702

    PubMed Central  PubMed  CAS  Google Scholar 

  105. Yang Z, Zhou L, Wu LM, Lai MC, Xie HY, Zhang F, Zheng SS (2011) Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol 18:1243–1250

    PubMed  Google Scholar 

  106. Liu Y et al (2012) A genetic variant in long non-coding RNA HULC contributes to risk of HBV-related hepatocellular carcinoma in a Chinese population. PLoS ONE 7:e35145

    PubMed Central  PubMed  CAS  Google Scholar 

  107. Golding MC, Magri LS, Zhang L, Lalone SA, Higgins MJ, Mann MR (2011) Depletion of Kcnq1ot1 non-coding RNA does not affect imprinting maintenance in stem cells. Development 138:3667–3678

    PubMed Central  PubMed  CAS  Google Scholar 

  108. Nakano S et al (2006) Expression profile of LIT1/KCNQ1OT1 and epigenetic status at the KvDMR1 in colorectal cancers. Cancer Sci 97:1147–1154

    PubMed  CAS  Google Scholar 

  109. Gutschner T et al (2013) The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 73:1180–1189

    PubMed Central  PubMed  CAS  Google Scholar 

  110. 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

    PubMed  Google Scholar 

  111. Lee GL, Dobi A, Srivastava S (2011) Prostate cancer: diagnostic performance of the PCA3 urine test. Nat Rev Urol 8:123–124

    PubMed  Google Scholar 

  112. Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465:1033–1038

    PubMed Central  PubMed  CAS  Google Scholar 

  113. Colley SM, Leedman PJ (2011) Steroid receptor RNA activator—a nuclear receptor coregulator with multiple partners: Insights and challenges. Biochimie 93:1966–1972

    PubMed  CAS  Google Scholar 

  114. Cooper C, Guo J, Yan Y, Chooniedass-Kothari S, Hube F, Hamedani MK, Murphy LC, Myal Y, Leygue E (2009) Increasing the relative expression of endogenous non-coding steroid receptor RNA activator (SRA) in human breast cancer cells using modified oligonucleotides. Nucleic Acids Res 37:4518–4531

    PubMed Central  PubMed  CAS  Google Scholar 

  115. Redon S, Zemp I, Lingner J (2013) A three-state model for the regulation of telomerase by TERRA and hnRNPA1. Nucleic Acids Res 41:9117–9128

    PubMed Central  PubMed  CAS  Google Scholar 

  116. Ritter O, Haase H, Schulte HD, Lange PE, Morano I (1999) Remodeling of the hypertrophied human myocardium by cardiac bHLH transcription factors. J Cell Biochem 74:551–561

    PubMed  CAS  Google Scholar 

  117. Ishii N et al (2006) Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction. J Hum Genet 51:1087–1099

    PubMed  CAS  Google Scholar 

  118. Rapicavoli NA, Poth EM, Blackshaw S (2010) The long noncoding RNA RNCR2 directs mouse retinal cell specification. BMC Dev Biol 10:49

    PubMed Central  PubMed  Google Scholar 

  119. Haddad F, Bodell PW, Qin AX, Giger JM, Baldwin KM (2003) Role of antisense RNA in coordinating cardiac myosin heavy chain gene switching. J Biol Chem 278:37132–37138

    PubMed  CAS  Google Scholar 

  120. Chubb JE, Bradshaw NJ, Soares DC, Porteous DJ, Millar JK (2008) The DISC locus in psychiatric illness. Mol Psychiatry 13:36–64

    PubMed  CAS  Google Scholar 

  121. Scheele C et al (2007) Altered regulation of the PINK1 locus: a link between type 2 diabetes and neurodegeneration? FASEB J 21:3653–3665

    PubMed  CAS  Google Scholar 

  122. Chen WL, Lin JW, Huang HJ, Wang SM, Su MT, Lee-Chen GJ, Chen CM, Hsieh-Li HM (2008) SCA8 mRNA expression suggests an antisense regulation of KLHL1 and correlates to SCA8 pathology. Brain Res 1233:176–184

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We apologize to all scientists whose important work of lncRNAs could not be cited in this review. The German Research Foundation (DFG MA-5028/1–3, LU-435/15-1) supports our work. We also receive support from the ECRC, a joint cooperation between the Max-Delbrück-Center for Molecular Medicine (MDC) and the Medical Faculty of the Charité.

Conflict of interest

The authors declare no interest conflicts.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Philipp G. Maass.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maass, P.G., Luft, F.C. & Bähring, S. Long non-coding RNA in health and disease. J Mol Med 92, 337–346 (2014). https://doi.org/10.1007/s00109-014-1131-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-014-1131-8

Keywords

Navigation