Home LiteratureArticle Details
PMID: 27007508 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Mechanisms of long noncoding RNA function in development and disease.

Cellular and molecular life sciences : CMLS ·Vol. 73 ·No. 13 ·2016-00-00 ·Pages 2491-509

Schmitz SU, Grote P, Herrmann BG

Abstract

Since decades it has been known that non-protein-coding RNAs have important cellular functions. Deep sequencing recently facilitated the discovery of thousands of novel transcripts, now classified as long noncoding RNAs (lncRNAs), in many vertebrate and invertebrate species. LncRNAs are involved in a wide range of cellular mechanisms, from almost all aspects of gene expression to protein translation and stability. Recent findings implicate lncRNAs as key players of cellular differentiation, cell lineage choice, organogenesis and tissue homeostasis. Moreover, lncRNAs are involved in pathological conditions such as cancer and cardiovascular disease, and therefore provide novel biomarkers and pharmaceutical targets. Here we discuss examples illustrating the versatility of lncRNAs in gene control, development and differentiation, as well as in human disease.

Keywords
Cancer Cardiovascular disease Chromatin Differentiation Epigenetics Gene regulation Genome organization LncRNA
MeSH Terms
Animals Cardiovascular Diseases/genetics,metabolism,pathology Chromatin Assembly and Disassembly DNA Methylation Epigenesis, Genetic Gene Expression Regulation Histone Code Humans Neoplasms/genetics,metabolism,pathology RNA, Long Noncoding/analysis,genetics,metabolism
Chemicals
RNA, Long Noncoding
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Schmitz Sandra U
Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195, Berlin, Germany. [email protected].
Grote Phillip
Institute of Cardiovascular Regeneration, Center for Molecular Medicine, Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
Herrmann Bernhard G
Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195, Berlin, Germany. [email protected]. | Institute for Medical Genetics, Campus Benjamin Franklin, Charite-University Medicine Berlin, Hindenburgdamm 30, 12203, Berlin, Germany. [email protected].
References (183)
183 references, click to expand
  1. Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells.
    Nat Struct Mol Biol. 2013 Sep;20(9):1131-9 PMID: 23934149
  2. p50-associated COX-2 extragenic RNA (PACER) activates COX-2 gene expression by occluding repressive NF-κB complexes.
    Elife. 2014 Apr 29;3:e01776 PMID: 24843008
  3. A long noncoding RNA protects the heart from pathological hypertrophy.
    Nature. 2014 Oct 2;514(7520):102-106 PMID: 25119045
  4. Discovery, Annotation, and Functional Analysis of Long Noncoding RNAs Controlling Cell-Cycle Gene Expression and Proliferation in Breast Cancer Cells.
    Mol Cell. 2015 Aug 20;59(4):698-711 PMID: 26236012
  5. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a.
    Mol Cell. 2010 Jun 11;38(5):662-74 PMID: 20541999
  6. Integration of genome-wide approaches identifies lncRNAs of adult neural stem cells and their progeny in vivo.
    Cell Stem Cell. 2013 May 2;12(5):616-28 PMID: 23583100
  7. Targeted disruption of Hotair leads to homeotic transformation and gene derepression.
    Cell Rep. 2013 Oct 17;5(1):3-12 PMID: 24075995
  8. Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation.
    EMBO J. 2014 May 2;33(9):981-93 PMID: 24705786
  9. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses.
    Genes Dev. 2011 Sep 15;25(18):1915-27 PMID: 21890647
  10. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression.
    Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11667-72 PMID: 19571010
  11. Control of somatic tissue differentiation by the long non-coding RNA TINCR.
    Nature. 2013 Jan 10;493(7431):231-5 PMID: 23201690
  12. Advances in long noncoding RNAs: identification, structure prediction and function annotation.
    Brief Funct Genomics. 2016 Jan;15(1):38-46 PMID: 26072035
  13. Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs.
    Science. 1995 Apr 21;268(5209):415-7 PMID: 7536344
  14. Selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) for direct, versatile and accurate RNA structure analysis.
    Nat Protoc. 2015 Nov;10(11):1643-69 PMID: 26426499
  15. Review toward all RNA structures, concisely.
    Biopolymers. 2015 Aug;103(8):438-48 PMID: 25546503
  16. Inhibiting gene expression at transcription start sites in chromosomal DNA with antigene RNAs.
    Nat Chem Biol. 2005 Sep;1(4):216-22 PMID: 16408038
  17. The four dimensions of noncoding RNA conservation.
    Trends Genet. 2014 Apr;30(4):121-3 PMID: 24613441
  18. DNMT1-associated long non-coding RNAs regulate global gene expression and DNA methylation in colon cancer.
    Hum Mol Genet. 2015 Nov 1;24(21):6240-53 PMID: 26307088
  19. Message and non-message sequences adjacent to poly(A) in steady state heterogeneous nuclear RNA of HeLa cells.
    Cell. 1976 Mar;7(3):429-37 PMID: 59633
  20. The abundance of short proteins in the mammalian proteome.
    PLoS Genet. 2006 Apr;2(4):e52 PMID: 16683031
  21. Specific expression of long noncoding RNAs in the mouse brain.
    Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):716-21 PMID: 18184812
  22. The IncRNAs PCGEM1 and PRNCR1 are not implicated in castration resistant prostate cancer.
    Oncotarget. 2014 Mar 30;5(6):1434-8 PMID: 24727738
  23. An atlas of active enhancers across human cell types and tissues.
    Nature. 2014 Mar 27;507(7493):455-461 PMID: 24670763
  24. Identification of a novel gene NCRMS on chromosome 12q21 with differential expression between rhabdomyosarcoma subtypes.
    Oncogene. 2002 May 2;21(19):3029-37 PMID: 12082533
  25. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs.
    Nature. 2002 Dec 5;420(6915):563-73 PMID: 12466851
  26. The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse.
    Dev Cell. 2013 Jan 28;24(2):206-14 PMID: 23369715
  27. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response.
    Cell. 2010 Aug 6;142(3):409-19 PMID: 20673990
  28. A functional genomic approach identifies FAL1 as an oncogenic long noncoding RNA that associates with BMI1 and represses p21 expression in cancer.
    Cancer Cell. 2014 Sep 8;26(3):344-357 PMID: 25203321
  29. Nuclear Fractionation Reveals Thousands of Chromatin-Tethered Noncoding RNAs Adjacent to Active Genes.
    Cell Rep. 2015 Aug 18;12(7):1089-98 PMID: 26257179
  30. Long noncoding RNAs with enhancer-like function in human cells.
    Cell. 2010 Oct 1;143(1):46-58 PMID: 20887892
  31. Genomic analysis of mouse retinal development.
    PLoS Biol. 2004 Sep;2(9):E247 PMID: 15226823
  32. Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
    Circulation. 2015 Apr 7;131(14):1278-1290 PMID: 25739401
  33. linc-HOXA1 is a noncoding RNA that represses Hoxa1 transcription in cis.
    Genes Dev. 2013 Jun 1;27(11):1260-71 PMID: 23723417
  34. The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3.
    Nature. 2015 May 14;521(7551):232-6 PMID: 25915022
  35. Transcriptome sequencing during mouse brain development identifies long non-coding RNAs functionally involved in neurogenic commitment.
    EMBO J. 2013 Dec 11;32(24):3145-60 PMID: 24240175
  36. The evolution of lncRNA repertoires and expression patterns in tetrapods.
    Nature. 2014 Jan 30;505(7485):635-40 PMID: 24463510
  37. A micropeptide encoded by a putative long noncoding RNA regulates muscle performance.
    Cell. 2015 Feb 12;160(4):595-606 PMID: 25640239
  38. A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation by blocking IMP2-mediated mRNA translation.
    Dev Cell. 2015 Jul 27;34(2):181-91 PMID: 26143994
  39. Intergenic transcription and transinduction of the human beta-globin locus.
    Genes Dev. 1997 Oct 1;11(19):2494-509 PMID: 9334315
  40. Genome-wide identification of polycomb-associated RNAs by RIP-seq.
    Mol Cell. 2010 Dec 22;40(6):939-53 PMID: 21172659
  41. A LncRNA-MAF:MAFB transcription factor network regulates epidermal differentiation.
    Dev Cell. 2015 Mar 23;32(6):693-706 PMID: 25805135
  42. Linking RNA biology to lncRNAs.
    Genome Res. 2015 Oct;25(10):1456-65 PMID: 26430155
  43. lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs.
    Nature. 2013 Aug 29;500(7464):598-602 PMID: 23945587
  44. Noncoding RNA NORAD Regulates Genomic Stability by Sequestering PUMILIO Proteins.
    Cell. 2016 Jan 14;164(1-2):69-80 PMID: 26724866
  45. Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the Inactive X Chromosome.
    Mol Cell. 2014 Jan 23;53(2):301-16 PMID: 24462204
  46. A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster.
    Blood. 2009 Mar 12;113(11):2526-34 PMID: 19144990
  47. The mRNA-like noncoding RNA Gomafu constitutes a novel nuclear domain in a subset of neurons.
    J Cell Sci. 2007 Aug 1;120(Pt 15):2498-506 PMID: 17623775
  48. Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss.
    Genes Dev. 2016 Jan 1;30(1):34-51 PMID: 26701265
  49. 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. 2007 Apr 15;67(8):3963-9 PMID: 17440112
  50. Decreased expression of long non-coding RNA NBAT-1 is associated with poor prognosis in patients with clear cell renal cell carcinoma.
    Int J Clin Exp Pathol. 2015 Apr 01;8(4):3765-74 PMID: 26097558
  51. The NeST long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-γ locus.
    Cell. 2013 Feb 14;152(4):743-54 PMID: 23415224
  52. Multiple knockout mouse models reveal lincRNAs are required for life and brain development.
    Elife. 2013 Dec 31;2:e01749 PMID: 24381249
  53. Malat1 is not an essential component of nuclear speckles in mice.
    RNA. 2012 Aug;18(8):1487-99 PMID: 22718948
  54. Landscape of transcription in human cells.
    Nature. 2012 Sep 6;489(7414):101-8 PMID: 22955620
  55. Parental imprinting of the mouse H19 gene.
    Nature. 1991 May 9;351(6322):153-5 PMID: 1709450
  56. The lncRNA Neat1 is required for corpus luteum formation and the establishment of pregnancy in a subpopulation of mice.
    Development. 2014 Dec;141(23):4618-27 PMID: 25359727
  57. CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis.
    J Mol Cell Cardiol. 2015 Dec;89(Pt A):98-112 PMID: 26423156
  58. Requirement for Xist in X chromosome inactivation.
    Nature. 1996 Jan 11;379(6561):131-7 PMID: 8538762
  59. Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes.
    Cell. 2011 Nov 11;147(4):789-802 PMID: 22056041
  60. Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2.
    Genome Biol. 2013;14(9):R104 PMID: 24070194
  61. Long noncoding RNAs are rarely translated in two human cell lines.
    Genome Res. 2012 Sep;22(9):1646-57 PMID: 22955977
  62. Long noncoding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A.
    Mol Cell. 2014 Aug 21;55(4):604-14 PMID: 25087872
  63. Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and development.
    RNA Biol. 2012 Aug;9(8):1076-87 PMID: 22858678
  64. The lncRNA DEANR1 facilitates human endoderm differentiation by activating FOXA2 expression.
    Cell Rep. 2015 Apr 7;11(1):137-48 PMID: 25843708
  65. The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo.
    Cell. 2015 Apr 9;161(2):319-32 PMID: 25843629
  66. Definition of the minimal requirements within the human beta-globin gene and the dominant control region for high level expression.
    EMBO J. 1990 Jan;9(1):233-40 PMID: 2295312
  67. Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution.
    Cell. 2011 Dec 23;147(7):1537-50 PMID: 22196729
  68. Disruption of imprinting caused by deletion of the H19 gene region in mice.
    Nature. 1995 May 4;375(6526):34-9 PMID: 7536897
  69. Long non-coding RNAs as a source of new peptides.
    Elife. 2014 Sep 16;3:e03523 PMID: 25233276
  70. Jpx RNA activates Xist by evicting CTCF.
    Cell. 2013 Jun 20;153(7):1537-51 PMID: 23791181
  71. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells.
    Cancer Res. 2013 Feb 1;73(3):1180-9 PMID: 23243023
  72. Chromosomes. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation.
    Science. 2015 Jul 17;349(6245): PMID: 26089354
  73. eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci.
    Mol Cell. 2013 Sep 12;51(5):606-17 PMID: 23993744
  74. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression.
    Genome Res. 2012 Sep;22(9):1775-89 PMID: 22955988
  75. Coordinated control of senescence by lncRNA and a novel T-box3 co-repressor complex.
    Elife. 2014 May 29;3: PMID: 24876127
  76. Noncoding transcription at enhancers: general principles and functional models.
    Annu Rev Genet. 2012;46:1-19 PMID: 22905871
  77. Comparison of splice sites reveals that long noncoding RNAs are evolutionarily well conserved.
    RNA. 2015 May;21(5):801-12 PMID: 25802408
  78. Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction.
    J Hum Genet. 2006;51(12):1087-1099 PMID: 17066261
  79. Noncoding RNA and Polycomb recruitment.
    RNA. 2013 Apr;19(4):429-42 PMID: 23431328
  80. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs.
    Cell. 2007 Jun 29;129(7):1311-23 PMID: 17604720
  81. A comparative encyclopedia of DNA elements in the mouse genome.
    Nature. 2014 Nov 20;515(7527):355-64 PMID: 25409824
  82. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis.
    Nature. 2010 Apr 15;464(7291):1071-6 PMID: 20393566
  83. MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures.
    Nat Commun. 2015 Jul 24;6:7743 PMID: 26205790
  84. The long non-coding RNA Dali is an epigenetic regulator of neural differentiation.
    Elife. 2014 Nov 21;3:e04530 PMID: 25415054
  85. WDR5, a complexed protein.
    Nat Struct Mol Biol. 2009 Jul;16(7):678-80 PMID: 19578375
  86. Braveheart, a long noncoding RNA required for cardiovascular lineage commitment.
    Cell. 2013 Jan 31;152(3):570-83 PMID: 23352431
  87. The lncRNA Firre anchors the inactive X chromosome to the nucleolus by binding CTCF and maintains H3K27me3 methylation.
    Genome Biol. 2015 Mar 12;16:52 PMID: 25887447
  88. Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers.
    Genome Biol. 2012 Aug 28;13(8):R75 PMID: 22929540
  89. Chromatin signatures at transcriptional start sites separate two equally populated yet distinct classes of intergenic long noncoding RNAs.
    Genome Biol. 2013 Nov 29;14(11):R131 PMID: 24289259
  90. The long noncoding RNA RMST interacts with SOX2 to regulate neurogenesis.
    Mol Cell. 2013 Aug 8;51(3):349-59 PMID: 23932716
  91. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression.
    Nature. 2011 Apr 7;472(7341):120-4 PMID: 21423168
  92. The steroid receptor RNA activator protein (SRAP) controls cancer cell migration/motility.
    FEBS Lett. 2015 Dec 21;589(24 Pt B):4010-8 PMID: 26581859
  93. The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation.
    Science. 2014 Apr 18;344(6181):310-3 PMID: 24744378
  94. Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure.
    Circ Res. 2014 May 9;114(10):1569-75 PMID: 24663402
  95. LincRNA-p21 regulates neointima formation, vascular smooth muscle cell proliferation, apoptosis, and atherosclerosis by enhancing p53 activity.
    Circulation. 2014 Oct 21;130(17):1452-1465 PMID: 25156994
  96. Long noncoding RNAs: Lessons from genomic imprinting.
    Biochim Biophys Acta. 2016 Jan;1859(1):102-11 PMID: 26004516
  97. Activating RNAs associate with Mediator to enhance chromatin architecture and transcription.
    Nature. 2013 Feb 28;494(7438):497-501 PMID: 23417068
  98. Multiple enhancers regulate Hoxd genes and the Hotdog LncRNA during cecum budding.
    Cell Rep. 2013 Oct 17;5(1):137-50 PMID: 24075990
  99. Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer.
    Nat Struct Mol Biol. 2013 Jul;20(7):908-13 PMID: 23728290
  100. An integrated encyclopedia of DNA elements in the human genome.
    Nature. 2012 Sep 6;489(7414):57-74 PMID: 22955616
  101. Toddler: an embryonic signal that promotes cell movement via Apelin receptors.
    Science. 2014 Feb 14;343(6172):1248636 PMID: 24407481
  102. Susceptibility to coronary artery disease and diabetes is encoded by distinct, tightly linked SNPs in the ANRIL locus on chromosome 9p.
    Hum Mol Genet. 2008 Mar 15;17(6):806-14 PMID: 18048406
  103. A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics.
    Elife. 2013 Jul 23;2:e00762 PMID: 23898399
  104. The long noncoding RNA RNCR2 directs mouse retinal cell specification.
    BMC Dev Biol. 2010 May 11;10:49 PMID: 20459797
  105. Rmst is a novel marker for the mouse ventral mesencephalic floor plate and the anterior dorsal midline cells.
    PLoS One. 2010 Jan 08;5(1):e8641 PMID: 20062813
  106. PARTICLE, a Triplex-Forming Long ncRNA, Regulates Locus-Specific Methylation in Response to Low-Dose Irradiation.
    Cell Rep. 2015 Apr 21;11(3):474-85 PMID: 25900080
  107. Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs.
    Eur Heart J. 2015 Feb 7;36(6):353-68a PMID: 24786300
  108. Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre.
    Nat Struct Mol Biol. 2014 Feb;21(2):198-206 PMID: 24463464
  109. Toward a consensus on the binding specificity and promiscuity of PRC2 for RNA.
    Mol Cell. 2015 Feb 5;57(3):552-8 PMID: 25601759
  110. Circular RNAs are a large class of animal RNAs with regulatory potency.
    Nature. 2013 Mar 21;495(7441):333-8 PMID: 23446348
  111. Long noncoding RNAs are spatially correlated with transcription factors and regulate lung development.
    Genes Dev. 2014 Jun 15;28(12):1363-79 PMID: 24939938
  112. Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors.
    EMBO J. 2012 Feb 1;31(3):522-33 PMID: 22193719
  113. Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs.
    Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12264-9 PMID: 25071214
  114. GENCODE: the reference human genome annotation for The ENCODE Project.
    Genome Res. 2012 Sep;22(9):1760-74 PMID: 22955987
  115. Genome-wide mapping and characterization of Notch-regulated long noncoding RNAs in acute leukemia.
    Cell. 2014 Jul 31;158(3):593-606 PMID: 25083870
  116. Enhancer RNA facilitates NELF release from immediate early genes.
    Mol Cell. 2014 Oct 2;56(1):29-42 PMID: 25263592
  117. Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain.
    Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):6855-62 PMID: 26034286
  118. Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes.
    Genes Dev. 2010 Oct 15;24(20):2264-9 PMID: 20952535
  119. LincRNA-p21 activates p21 in cis to promote Polycomb target gene expression and to enforce the G1/S checkpoint.
    Mol Cell. 2014 Jun 5;54(5):777-90 PMID: 24857549
  120. Activation of paternally expressed genes and perinatal death caused by deletion of the Gtl2 gene.
    Development. 2010 Aug;137(16):2643-52 PMID: 20610486
  121. lncRNA directs cooperative epigenetic regulation downstream of chemokine signals.
    Cell. 2014 Nov 20;159(5):1110-1125 PMID: 25416949
  122. The lncRNA Malat1 is dispensable for mouse development but its transcription plays a cis-regulatory role in the adult.
    Cell Rep. 2012 Jul 26;2(1):111-23 PMID: 22840402
  123. Long noncoding RNAs in organogenesis: making the difference.
    Trends Genet. 2015 Jun;31(6):329-35 PMID: 25743487
  124. Long non-coding RNAs and enhancers.
    Curr Opin Genet Dev. 2011 Apr;21(2):194-8 PMID: 21330130
  125. The long noncoding RNA Pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells.
    Cell Stem Cell. 2015 Apr 2;16(4):439-447 PMID: 25800779
  126. The " NF-ĸ B interacting long noncoding RNA" ( NKILA) transcript is antisense to cancer-associated gene PMEPA1.
    F1000Res. 2015 Apr 22;4:96 PMID: 26069731
  127. Xist-deficient mice are defective in dosage compensation but not spermatogenesis.
    Genes Dev. 1997 Jan 15;11(2):156-66 PMID: 9009199
  128. Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice.
    Nature. 2010 Mar 18;464(7287):409-12 PMID: 20173736
  129. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease.
    J Mol Cell Cardiol. 2014 Nov;76:55-70 PMID: 25149110
  130. Expression of Xist during mouse development suggests a role in the initiation of X chromosome inactivation.
    Cell. 1993 Jan 29;72(2):171-82 PMID: 8425217
  131. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome.
    Science. 2008 Oct 31;322(5902):750-6 PMID: 18974356
  132. Role of histone H3 lysine 27 methylation in X inactivation.
    Science. 2003 Apr 4;300(5616):131-5 PMID: 12649488
  133. DNMT1-interacting RNAs block gene-specific DNA methylation.
    Nature. 2013 Nov 21;503(7476):371-6 PMID: 24107992
  134. Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature.
    Nat Commun. 2014 Dec 19;5:5812 PMID: 25524025
  135. The risk-associated long noncoding RNA NBAT-1 controls neuroblastoma progression by regulating cell proliferation and neuronal differentiation.
    Cancer Cell. 2014 Nov 10;26(5):722-37 PMID: 25517750
  136. Downregulated LncRNA-ANCR promotes osteoblast differentiation by targeting EZH2 and regulating Runx2 expression.
    Biochem Biophys Res Commun. 2013 Mar 22;432(4):612-7 PMID: 23438432
  137. Widespread transcription at neuronal activity-regulated enhancers.
    Nature. 2010 May 13;465(7295):182-7 PMID: 20393465
  138. Erratum: Structural imprints in vivo decode RNA regulatory mechanisms.
    Nature. 2015 Nov 12;527(7577):264 PMID: 26416736
  139. Long Noncoding RNA Ceruloplasmin Promotes Cancer Growth by Altering Glycolysis.
    Cell Rep. 2015 Dec 22;13(11):2395-2402 PMID: 26686630
  140. Long non-coding RNA ANRIL (CDKN2B-AS) is induced by the ATM-E2F1 signaling pathway.
    Cell Signal. 2013 May;25(5):1086-95 PMID: 23416462
  141. The H19 long noncoding RNA gives rise to microRNAs miR-675-3p and miR-675-5p to promote skeletal muscle differentiation and regeneration.
    Genes Dev. 2014 Mar 1;28(5):491-501 PMID: 24532688
  142. Gene activation-associated long noncoding RNAs function in mouse preimplantation development.
    Development. 2015 Mar 1;142(5):910-20 PMID: 25633350
  143. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation.
    Mol Cell. 2010 Sep 24;39(6):925-38 PMID: 20797886
  144. Locus-specific targeting to the X chromosome revealed by the RNA interactome of CTCF.
    Mol Cell. 2015 Jan 22;57(2):361-75 PMID: 25578877
  145. Natural RNA circles function as efficient microRNA sponges.
    Nature. 2013 Mar 21;495(7441):384-8 PMID: 23446346
  146. Long noncoding RNAs: cellular address codes in development and disease.
    Cell. 2013 Mar 14;152(6):1298-307 PMID: 23498938
  147. Evf2 lncRNA/BRG1/DLX1 interactions reveal RNA-dependent inhibition of chromatin remodeling.
    Development. 2015 Aug 1;142(15):2641-52 PMID: 26138476
  148. Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin.
    Mol Cell. 2014 Jan 23;53(2):290-300 PMID: 24374312
  149. Rise of the RNA machines: exploring the structure of long non-coding RNAs.
    J Mol Biol. 2013 Oct 9;425(19):3731-46 PMID: 23467124
  150. The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex.
    Nat Genet. 2013 Nov;45(11):1392-8 PMID: 24076601
  151. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.
    Nature. 2009 Mar 12;458(7235):223-7 PMID: 19182780
  152. The landscape of long noncoding RNAs in the human transcriptome.
    Nat Genet. 2015 Mar;47(3):199-208 PMID: 25599403
  153. Regulation of the ESC transcriptome by nuclear long noncoding RNAs.
    Genome Res. 2015 Sep;25(9):1336-46 PMID: 26048247
  154. The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing.
    Mol Psychiatry. 2014 Apr;19(4):486-94 PMID: 23628989
  155. Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry.
    Nat Neurosci. 2009 Aug;12(8):1020-7 PMID: 19620975
  156. Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells.
    Nat Genet. 2012 Mar 04;44(4):398-405, S1-2 PMID: 22387999
  157. Transcription initiation platforms and GTF recruitment at tissue-specific enhancers and promoters.
    Nat Struct Mol Biol. 2011 Jul 17;18(8):956-63 PMID: 21765417
  158. Comprehensive Genomic Characterization of Long Non-coding RNAs across Human Cancers.
    Cancer Cell. 2015 Oct 12;28(4):529-540 PMID: 26461095
  159. Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all.
    Nat Rev Mol Cell Biol. 2006 Sep;7(9):667-77 PMID: 16921403
  160. Structural and functional differences in the long non-coding RNA hotair in mouse and human.
    PLoS Genet. 2011 May;7(5):e1002071 PMID: 21637793
  161. A network comprising short and long noncoding RNAs and RNA helicase controls mouse retina architecture.
    Nat Commun. 2015 Jun 04;6:7305 PMID: 26041499
  162. Physiological roles of long noncoding RNAs: insight from knockout mice.
    Trends Cell Biol. 2014 Oct;24(10):594-602 PMID: 25022466
  163. The lncRNA MIR31HG regulates p16(INK4A) expression to modulate senescence.
    Nat Commun. 2015 Apr 24;6:6967 PMID: 25908244
  164. Airn transcriptional overlap, but not its lncRNA products, induces imprinted Igf2r silencing.
    Science. 2012 Dec 14;338(6113):1469-72 PMID: 23239737
  165. Opposing Roles for the lncRNA Haunt and Its Genomic Locus in Regulating HOXA Gene Activation during Embryonic Stem Cell Differentiation.
    Cell Stem Cell. 2015 May 7;16(5):504-16 PMID: 25891907
  166. Chromatin Architecture of the Pitx2 Locus Requires CTCF- and Pitx2-Dependent Asymmetry that Mirrors Embryonic Gut Laterality.
    Cell Rep. 2015 Oct 13;13(2):337-49 PMID: 26411685
  167. Suppression of progenitor differentiation requires the long noncoding RNA ANCR.
    Genes Dev. 2012 Feb 15;26(4):338-43 PMID: 22302877
  168. The long non-coding RNA Fendrr links epigenetic control mechanisms to gene regulatory networks in mammalian embryogenesis.
    RNA Biol. 2013 Oct;10(10):1579-85 PMID: 24036695
  169. Paraspeckles are subpopulation-specific nuclear bodies that are not essential in mice.
    J Cell Biol. 2011 Apr 4;193(1):31-9 PMID: 21444682
  170. Considerations when investigating lncRNA function in vivo.
    Elife. 2014 Aug 14;3:e03058 PMID: 25124674
  171. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer.
    Oncogene. 2003 Sep 11;22(39):8031-41 PMID: 12970751
  172. A cytoplasmic NF-κB interacting long noncoding RNA blocks IκB phosphorylation and suppresses breast cancer metastasis.
    Cancer Cell. 2015 Mar 9;27(3):370-81 PMID: 25759022
  173. Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins.
    Cell. 2013 Jul 3;154(1):240-51 PMID: 23810193
  174. The long noncoding RNA lncTCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling.
    Cell Stem Cell. 2015 Apr 2;16(4):413-25 PMID: 25842979
  175. The product of the H19 gene may function as an RNA.
    Mol Cell Biol. 1990 Jan;10(1):28-36 PMID: 1688465
  176. PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer.
    Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12216-21 PMID: 11050243
  177. Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation.
    Nature. 2013 Jun 27;498(7455):516-20 PMID: 23728302
  178. lincRNAs act in the circuitry controlling pluripotency and differentiation.
    Nature. 2011 Aug 28;477(7364):295-300 PMID: 21874018
  179. Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity.
    Nat Genet. 2013 May;45(5):513-7 PMID: 23563609
  180. Disruption of Visc-2, a Brain-Expressed Conserved Long Noncoding RNA, Does Not Elicit an Overt Anatomical or Behavioral Phenotype.
    Cereb Cortex. 2015 Oct;25(10):3572-85 PMID: 25209608
  181. An evolutionarily conserved long noncoding RNA TUNA controls pluripotency and neural lineage commitment.
    Mol Cell. 2014 Mar 20;53(6):1005-19 PMID: 24530304
  182. Unexpected selection to retain high GC content and splicing enhancers within exons of multiexonic lncRNA loci.
    RNA. 2015 Mar;21(3):333-46 PMID: 25589248
  183. Essential role of lncRNA binding for WDR5 maintenance of active chromatin and embryonic stem cell pluripotency.
    Elife. 2014 Feb 12;3:e02046 PMID: 24521543
Article Info
Journal
Cellular and molecular life sciences : CMLS
Abbr.
Cell Mol Life Sci
ISSN
1420-9071
DOI
10.1007/s00018-016-2174-5
Email
[email protected]
[email protected]
Published
2016-00-00
Epub
2016-00-23
Pages
2491-509
Language
English
Region
Switzerland
NLM ID
9705402
PMCID
PMC4894931
Subset
IM
External Links
PubMed source DOI: 10.1007/s00018-016-2174-5 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2