A novel molecular mechanism in human genetic disease: A DNA repeat-derived lncRNA point-of-view

RNA Biology

Volumn 9, Issue 10, 2012, Pages 1211-1217

  Cabianca, Daphne S ^a   Casa, Valentina ^a,b   Gabellini, Davide ^a  

^a DULBECCO TELETHON INSTITUTE   (Italy)

^b VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

Author keywords

Chromatin; Muscular dystrophy; Non protein coding RNA; Polycomb; Repetitive element; Trithorax

Indexed keywords

EID: 84868238247     PISSN: 15476286     EISSN: 15558584     Source Type: Journal    
DOI: 10.4161/rna.21922     Document Type: Note

References (94)

1. Mattick JS. Deconstructing the dogma: a new view of the evolution and genetic programming of complex organisms. Ann N Y Acad Sci 2009; 1178:29-46; PMID:19845626 ; ht tp://d x.doi.org/10.1111/j.1749-6632.2009.04991.x.
2. Moran VA, Perera RJ, Khalil AM. Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucleic Acids Res 2012; 40:6391-400; PMID:22492512; http://dx.doi.org/10.1093/nar/gks296.
3. Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, et al.; FANTOM Consortium; RIKEN Genome Exploration Research Group and Genome Science Group (Genome Network Project Core Group). The transcriptional landscape of the mammalian genome. Science 2005; 309:1559-63; PMID:16141072; http://dx.doi.org/ 10.1126/sci-en c e.1112 014.
4. Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet 2009; 10:155-9; PMID:19188922; http://dx.doi.org/10. 1038/nrg2521.
5. Kaikkonen MU, Lam MT, Glass CK. Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovasc Res 2011; 90:430-40; PMID:21558279; http://dx.doi.org/10.1093/cvr/cvr097.
6. Derrien T, Guigó R, Johnson R. The Long Non-Coding RNAs: A New (P)layer in the "Dark Matter". Front Genet 2011; 2:107; PMID:22303401.
7. Orom UA, Shiekhattar R. Noncoding RNAs and enhancers: complications of a long-distance relationship. Trends Genet 2011; 27:433-9; PMID:21831473; http://dx.doi.org/10.1016/j.tig.2011.06.009.
8. de Koning AP, Gu W, Castoe TA, Batzer MA, Pollock DD. Repetitive elements may comprise over two-thirds of the human genome. PLoS Genet 2011; 7:e1002384; PMID:22144907; http://dx.doi.org/10.1371/journal.pgen.1002384.
9. Mercer TR, Gerhardt DJ, Dinger ME, Crawford J, Trapnell C, Jeddeloh JA, et al. Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nat Biotechnol 2012; 30:99-104; PMID:22081020; http://dx.doi.org/10.1038/nbt.2024.
10. Spitale RC, Tsai MC, Chang HY. R NA templating the epigenome: long noncoding RNAs as molecular scaffolds. Epigenetics 2011; 6:539-43; PMID:21393997; http://dx.doi.org/10.4161/epi.6.5.15221.
11. Sanchez-Elsner T, Gou D, Kremmer E, Sauer F. Noncoding RNAs of trithorax response elements recruit Drosophila Ash1 to Ultrabithorax. Science 2006; 311:1118-23; PMID:16497925; http://dx.doi.org/10.1126/science.1117705.
12. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 2007; 129:1311-23; PMID:17604720; http://dx.doi.org/10. 1016/j. cell.2007.05.022.
13. Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 2008; 322:750-6; PMID:18974356; http://dx.doi.org/10.1126/sci-en c e.1163045.
14. Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, et al. Many human large intergenic noncoding RNAs associate with chro-matin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA 2009; 106:11667-72; PMID:19571010; http://dx.doi.org/10.1073/pnas.0904715106.
15. Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, et al. A long noncod-ing RNA maintains active chromatin to coordinate homeotic gene expression. Nature 2011; 472:120-4; PMID:21423168; http://dx.doi.org/10.1038/ nature09819.
16. Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 2011; 477:295-300; PMID:21874018; http://dx.doi.org/10.1038/nature10398.
17. Bertani S, Sauer S, Bolotin E, Sauer F. The non-coding RNA Mistral activates Hoxa6 and Hoxa7 expression and stem cell differentiation by recruiting MLL1 to chromatin. Mol Cell 2011; 43:1040-6; PMID:21925392; http://dx.doi.org/10.1016/j.mol-cel.2011.08.019.
18. Cabianca DS, Casa V, Bodega B, Xynos A, Ginelli E, Tanaka Y, et al. A long ncRNA links copy number variation to a polycomb/trithorax epigenetic switch in FSHD muscular dystrophy. Cell 2012; 149:819-31; PMID:22541069; http://dx.doi.org/10.1016/j. cell.2012.03.035.
19. Guil S, Soler M, Portela A, Carrère J, Fonalleras E, Gómez A, et al. Intronic RNAs mediate EZH2 regulation of epigenetic targets. Nat Struct Mol Biol 2012; 19:664-70; PMID:22659877; http://dx.doi.org/10.1038/nsmb. 2315.
20. Lyon MF. Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 1961; 190:372-3; PMID:13764598; http://dx.doi.org/10.1038/190372a0.
21. Lee JT. Gracefully ageing at 50, X-chromosome inactivation becomes a paradigm for RNA and chromatin control. Nat Rev Mol Cell Biol 2011; 12:815-26; PMID:22108600; http://dx.doi.org/10.1038/nrm3231.
22. Simon JA, Kingston RE. Mechanisms of polycomb gene silencing: knowns and unknowns. Nat Rev Mol Cell Biol 2009; 10:697-708; PMID:19738629.
23. Schuettengruber B, Martinez AM, Iovino N, Cavalli G. Trithorax group proteins: switching genes on and keeping them active. Nat Rev Mol Cell Biol 2011; 12:799-814; PMID:22108599; http://dx.doi.org/10.1038/nrm3230.
24. Martinez AM, Cavalli G. The role of polycomb group proteins in cell cycle regulation during development. Cell Cycle 2006; 5:1189-97; PMID:16721063; http://dx.doi.org/10.4161/cc.5.11.2781.
25. Sparmann A, van Lohuizen M. Polycomb silencers control cell fate, development and cancer. Nat Rev Cancer 2006; 6:846-56; PMID:17060944; http://dx.doi.org/10.1038/nrc1991.
26. Lin Y W, Chen HM, Fang JY. Gene silencing by the Polycomb group proteins and associations with cancer. Cancer Invest 2011; 29:187-95; PMID:21294604; http://dx.doi.org/10.3109/07357907.2010.512605.
27. Gieni RS, Hendzel MJ. Polycomb group protein gene silencing, non-coding RNA, stem cells, and cancer. Biochem Cell Biol 2009; 87:711-46; PMID:19898523; http://dx.doi.org/10.1139/O09-0 57.
28. Kanduri C, Whitehead J, Mohammad F. The long and the short of it: RNA-directed chromatin asymmetry in mammalian X-chromosome inactivation. FEBS Lett 2009; 583:857-64; PMID:19302783; http://dx.doi.org/10.1016/j.febslet.2009. 02.004.
29. Wutz A, Rasmussen TP, Jaenisch R. Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nat Genet 2002; 30:167-74; PMID:11780141; http://dx.doi.org/10.1038/ng820.
30. Jeon Y, Lee JT. YY1 tethers Xist RNA to the inactive X nucleation center. Cell 2011; 146:119-33; PMID:21729784; http://dx.doi.org/10.1016/j. cell.2011.06.026.
31. Schoeftner S, Sengupta AK, Kubicek S, Mechtler K, Spahn L, Koseki H, et al. Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing. EMBO J 2006; 25:3110-22; PMID:16763550; http://dx.doi.org/10.1038/sj.emboj.7601187.
32. Lee JT, Davidow LS, Warshawsky D. Tsix, a gene antisense to Xist at the X-inactivation centre. Nat Genet 1999; 21:400-4; PMID:10192391; http://dx.doi.org/10.1038/7734.
33. Sun BK, Deaton AM, Lee JT. A transient heterochro-matic state in Xist preempts X inactivation choice without RNA stabilization. Mol Cell 2006; 21:617-28; PMID:16507360; http://dx.doi.org/10.1016/j. molcel.2006.01.028.
34. Hogga I, Karch F. Transcription through the iab-7 cis-regulatory domain of the bithorax complex interferes with maintenance of Polycomb-mediated silencing. Development 2002; 129:4915-22; PMID:12397100.
35. Rank G, Prestel M, Paro R. Transcription through intergenic chromosomal memory elements of the Drosophila bithorax complex correlates with an epigenetic switch. Mol Cell Biol 2002; 22:8026-34; PMID:12391168; http://dx.doi.org/10. 1128/MCB.22.22.8026-8034.2002.
36. Schmitt S, Prestel M, Paro R. Intergenic transcription through a polycomb group response element counteracts silencing. Genes Dev 2005; 19:697-708; PMID:15741315; http://dx.doi.org/10.1101/gad.326205.
37. Sessa L, Breiling A, Lavorgna G, Silvestri L, Casari G, Orlando V. Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colin-ear activation of the human HOXA cluster. RNA 2007; 13:223-39; PMID:17185360; http://dx.doi.org/10.1261/rna.266707.
38. Flanigan KM, Coffeen CM, Sexton L, Stauffer D, Brunner S, Leppert MF. Genetic characterization of a large, historically significant Utah kindred with facioscapulohumeral dystrophy. Neuromuscul Disord 2001; 11:525-9; PMID:11525880; http://dx.doi.org/10.1016/S0960-8966(01)00201-2.
39. Cabianca DS, Gabellini D. The cell biology of disease: FSHD: copy number variations on the theme of muscular dystrophy. J Cell Biol 2010; 191:1049-60; PMID:21149563; http://dx.doi.org/10.1083/jcb.201007028.
40. Hewitt JE, Lyle R, Clark LN, Valleley EM, Wright TJ, Wijmenga C, et al. Analysis of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular dystrophy. Hum Mol Genet 1994; 3:1287-95; PMID:7987304; http://dx.doi.org/10.1093/hmg/3.8.1287.
41. Winokur ST, Bengtsson U, Feddersen J, Mathews KD, Weiffenbach B, Bailey H, et al. The DNA rearrangement associated with facioscapulohumeral muscular dystrophy involves a heterochromatin-associat-ed repetitive element: implications for a role of chromatin structure in the pathogenesis of the disease. Chromosome Res 1994; 2:225-34; PMID:8069466; http://dx.doi.org/10.1007/ BF01553323.
42. Wijmenga C, Hewitt JE, Sandkuijl LA, Clark LN, Wright TJ, Dauwerse HG, et al. Chromosome 4q DNA rearrangements associated with facioscapulo-humeral muscular dystrophy. Nat Genet 1992; 2:26-30; PMID:1363881; http://dx.doi.org/10. 1038/ng0992-26.
43. van Deutekom JC, Wijmenga C, van Tienhoven EA, Gruter AM, Hewitt JE, Padberg GW, et al. FSHD associated DNA rearrangements are due to deletions of integral copies of a 3.2 kb tandemly repeated unit. Hum Mol Genet 1993; 2:2037-42; PMID:8111371; http://dx.doi.org/10.1093/hmg/2.12.2037.
44. Chadwick BP. Macrosatellite epigenetics: the two faces of DXZ4 and D4Z4. Chromosoma 2009; 118:675-81; PMID:19690880; http://dx.doi.org/10.1007/s00412- 009-0233-5.
45. Giacalone J, Friedes J, Francke U. A novel GC-rich human macrosatellite VNTR in Xq24 is differentially methylated on active and inactive X chromosomes. Nat Genet 1992; 1:137-43; PMID:1302007; http://dx.doi.org/10.1038/ng0592-137.
46. Kogi M, Fukushige S, Lefevre C, Hadano S, Ikeda JE. A novel tandem repeat sequence located on human chromosome 4p: isolation and characterization. Genomics 1997; 42:278-83; PMID:9192848; http://dx.doi.org/10.1006/geno.1997. 4746.
47. Neguembor M V, Gabellini D. In junk we trust: repetitive DNA, epigenetics and facioscapulohumeral muscular dystrophy. Epigenomics 2010; 2:271-87; PMID:22121874; http://dx.doi.org/10.2217/epi.10.8.
48. van Overveld PG, Lemmers RJ, Sandkuijl LA, Enthoven L, Winokur ST, Bakels F, et al. Hypomethylation of D4Z4 in 4q-linked and non-4q-linked facioscapulohumeral muscular dystrophy. Nat Genet 2003; 35:315-7; PMID:14634647; http://dx.doi.org/10.1038/ng1262.
49. Bodega B, Ramirez GD, Grasser F, Cheli S, Brunelli S, Mora M, et al. Remodeling of the chromatin structure of the facioscapulohumeral muscular dystrophy (FSHD) locus and upregulation of FSHD-related gene 1 (FRG1) expression during human myogenic differentiation. BMC Biol 2009; 7:41; PMID:19607661; http://dx.doi.org/10.1186/1741-70 0 7-7-41.
50. Zeng W, de Greef JC, Chen YY, Chien R, Kong X, Gregson HC, et al. Specific loss of histone H3 lysine 9 trimethylation and HP1gamma/cohesin binding at D4Z4 repeats is associated with facioscapulohumeral dystrophy (FSHD). PLoS Genet 2009; 5:e1000559; PMID:19593370; http://dx.doi.org/10.1371/journal. pgen.1000559.
51. Petrov A, Pirozhkova I, Carnac G, Laoudj D, Lipinski M, Vassetzky YS. Chromatin loop domain organization within the 4q35 locus in facioscapulo-humeral dystrophy patients versus normal human myoblasts. Proc Natl Acad Sci USA 2006; 103:6982-7; PMID:16632607; http://dx.doi.org/10.1073/pn a s. 0 5112 35103.
52. Pirozhkova I, Petrov A, Dmitriev P, Laoudj D, Lipinski M, Vassetzky Y. A functional role for 4qA/B in the structural rearrangement of the 4q35 region and in the regulation of FRG1 and ANT1 in facioscapulohumeral dystrophy. PLoS ONE 2008; 3:e3389; PMID:18852887; http://dx.doi.org/10.1371/journal.pone.0003389.
53. Gabellini D, Green MR, Tupler R. Inappropriate gene activation in FSHD: a repressor complex binds a chromosomal repeat deleted in dystrophic muscle. Cell 2002; 110:339-48; PMID:12176321; http://dx.doi.org/10.1016/S0092-8674(02)00826- 7.
54. Lemmers RJ, van der Vliet PJ, Klooster R, Sacconi S, Camaño P, Dauwerse JG, et al. A unifying genetic model for facioscapulohumeral muscular dystrophy. Science 2010; 329:1650-3; PMID:20724583; http://d x.doi.org/10.1126/scienc e.1189 04 4.
55. Lemmers RJ, Osborn M, Haaf T, Rogers M, Frants RR, Padberg GW, et al. D4F104S1 deletion in facioscapulohumeral muscular dystrophy: pheno-type, size, and detection. Neurology 2003; 61:178-83; PMID:12874395; http://dx.doi.org/10. 1212/01. WNL.0000078889.51444.81.
56. Balog J, Thijssen PE, de Greef JC, Shah B, van Engelen BG, Yokomori K, et al. Correlation analysis of clinical parameters with epigenetic modifications in the DUX4 promoter in FSHD. Epigenetics 2012; 7:579-84; PMID:22522912; http://dx.doi.org/10.4161/epi.20001.
57. Duncan I W. Transvection effects in Drosophila. Annu Rev Genet 2002; 36:521-56; PMID:12429702; http://dx.doi.org/10.1146/annurev.genet.36.060402. 100441.
58. Stout K, van der Maarel S, Frants RR, Padberg GW, Ropers HH, Haaf T. Somatic pairing between subtelomeric chromosome regions: implications for human genetic disease? Chromosome Res 1999; 7:323-9; PMID:10515207; http://dx.doi.org/10.1023/A:1009287111661.
59. Goto K, Song MD, Lee JH, Arahata K. Genetic analysis of facioscapulohumeral muscular dystrophy (FSHD). Rinsho Shinkeigaku 1995; 35:1416-8; PMID:8752415.
60. Lunt PW, Jardine PE, Koch MC, Maynard J, Osborn M, Williams M, et al. Correlation between fragment size at D4F104S1 and age at onset or at wheelchair use, with a possible generational effect, accounts for much phenotypic variation in 4q35-facioscapu-lohumeral muscular dystrophy (FSHD). Hum Mol Genet 1995; 4:951-8; PMID:7633457; http://dx.doi.org/10.1093/hmg/4.5.951.
61. Zatz M, Marie SK, Passos-Bueno MR, Vainzof M, Campiotto S, Cerqueira A, et al. High proportion of new mutations and possible anticipation in Brazilian facioscapulohumeral muscular dystrophy families. Am J Hum Genet 1995; 56:99-105; PMID:7825608.
62. Tawil R, Forrester J, Griggs RC, Mendell J, Kissel J, McDermott M, et al.; The FSH-DY Group. Evidence for anticipation and association of deletion size with severity in facioscapulohumeral muscular dystrophy. Ann Neurol 1996; 39:744-8; PMID:8651646; http://dx.doi.org/10.1002/ana.410390610.
63. Hsu YD, Kao MC, Shyu WC, Lin JC, Huang NE, Sun HF, et al. Application of chromosome 4q35-qter marker (pFR-1) for DNA rearrangement of facioscapulohumeral muscular dystrophy patients in Taiwan. J Neurol Sci 1997; 149:73-9; PMID:9168169; http://dx.doi.org/10.1016/S0022-510X(97)05394-X.
64. Ricci E, Galluzzi G, Deidda G, Cacurri S, Colantoni L, Merico B, et al. Progress in the molecular diagnosis of facioscapulohumeral muscular dystrophy and correlation between the number of KpnI repeats at the 4q35 locus and clinical phenotype. Ann Neurol 1999; 45:751-7; PMID:10360767; http://dx.doi.org/10.1002/1531-8249(199906)45:6<751::AID-ANA9>3.0.CO;2-M.
65. Bumgarner SL, Neuert G, Voight BF, Symbor-Nagrabska A, Grisafi P, van Oudenaarden A, et al. Single-cell analysis reveals that noncoding RNAs contribute to clonal heterogeneity by modulating transcription factor recruitment. Mol Cell 2012; 45:470-82; PMID:22264825; http://dx.doi.org/10.1016/ j.molcel.2011.11.029.
66. Wagner EJ, Carpenter PB. Understanding the language of Lys36 methylation at histone H3. Nat Rev Mol Cell Biol 2012; 13:115-26; PMID:22266761; http://dx.doi.org/10.1038/nrm3274.
67. Kizer KO, Phatnani HP, Shibata Y, Hall H, Greenleaf AL, Strahl BD. A novel domain in Set2 mediates RNA polymerase II interaction and couples histone H3 K36 methylation with transcript elongation. Mol Cell Biol 2005; 25:3305-16; PMID:15798214; http://dx.doi.org/10.1128/MCB.25.8.3305-3316.2005.
68. Rao B, Shibata Y, Strahl BD, Lieb JD. Dimethylation of histone H3 at lysine 36 demarcates regulatory and nonregulatory chromatin genome-wide. Mol Cell Biol 2005; 25:9447-59; PMID:16227595; http://dx.doi.org/10.1128/MCB.25.21. 9447-9459.2005.
69. Kuo AJ, Cheung P, Chen K, Zee BM, Kioi M, Lauring J, et al. NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming. Mol Cell 2011; 44:609-20; PMID:22099308; http://dx.doi.org/10.1016/j.molcel.2011.08.042.
70. Carrozza MJ, Li B, Florens L, Suganuma T, Swanson SK, Lee KK, et al. Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell 2005; 123:581-92; PMID:16286007; http://dx.doi.org/10.1016/j.cell.2005.10.023.
71. Fnu S, Williamson EA, De Haro LP, Brenneman M, Wray J, Shaheen M, et al. Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining. Proc Natl Acad Sci USA 2011; 108:540-5; PMID:21187428; http://dx.doi.org/10.1073/pnas.1013571108.
72. Bender LB, Suh J, Carroll CR, Fong Y, Fingerman IM, Briggs SD, et al. MES-4: an autosome-associated histone methyltransferase that participates in silencing the X chromosomes in the C. elegans germ line. Development 2006; 133:3907-17; PMID:16968818; http://dx.doi.org/10.1242/dev.02584.
73. Wang GG, Cai L, Pasillas MP, Kamps MP. NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis. Nat Cell Biol 2007; 9:804-12; PMID:17589499; http://dx.doi.org/10.1038/ncb1608.
74. Yuan W, Xu M, Huang C, Liu N, Chen S, Zhu B. H3K36 methylation antagonizes PRC2-mediated H3K27 methylation. J Biol Chem 2011; 286:7983-9; PMID:21239496; http://dx.doi.org/10.1074/jbc. M110.194 0 2 7.
75. Norris J, Fan D, Aleman C, Marks JR, Futreal PA, Wiseman RW, et al. Identification of a new subclass of Alu DNA repeats which can function as estrogen receptor-dependent transcriptional enhancers. J Biol Chem 1995; 270:22777-82; PMID:7559405; http://dx.doi.org/10.1074/jbc.270.39.22777.
76. Speek M. Antisense promoter of human L1 ret-rotransposon drives transcription of adjacent cellular genes. Mol Cell Biol 2001; 21:1973-85; PMID:11238933; http://dx.doi.org/10.1128/MCB.21.6.1973-1985.2001.
77. Faulkner GJ, Kimura Y, Daub CO, Wani S, Plessy C, Irvine KM, et al. The regulated retrotranspo-son transcriptome of mammalian cells. Nat Genet 2009; 41:563-71; PMID:19377475; http://dx.doi.org/10.1038/ng.368.
78. Kaneko H, Dridi S, Tarallo V, Gelfand BD, Fowler BJ, Cho WG, et al. DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. Nature 2011; 471:325-30; PMID:21297615; http://dx.doi.org/10.1038/nature09830.
79. Shen S, Lin L, Cai JJ, Jiang P, Kenkel EJ, Stroik MR, et al. Widespread establishment and regulatory impact of Alu exons in human genes. Proc Natl Acad Sci USA 2011; 108:2837-42; PMID:21282640; http://dx.doi.org/10.1073/pnas. 1012834108.
80. Peters AH, Kubicek S, Mechtler K, O'Sullivan RJ, Derijck AA, Perez-Burgos L, et al. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol Cell 2003; 12:1577-89; PMID:14690609; http://dx.doi.org/10.1016/S1097-2765(03)00477-5.
81. de Napoles M, Mermoud JE, Wakao R, Tang YA, Endoh M, Appanah R, et al. Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. Dev Cell 2004; 7:663-76; PMID:15525528; http://dx.doi.org/10.1016/j.devcel.2004.10.005.
82. Day DS, Luquette LJ, Park PJ, Kharchenko PV. Estimating enrichment of repetitive elements from high-throughput sequence data. Genome Biol 2010; 11:R69; PMID:20584328; http://dx.doi.org/10.118 6/gb-2010-11-6-r 69.
83. Leeb M, Pasini D, Novatchkova M, Jaritz M, Helin K, Wutz A. Polycomb complexes act redundantly to repress genomic repeats and genes. Genes Dev 2010; 24:265-76; PMID:20123906; http://dx.doi.org/10.1101/gad.544410.
84. Costa FF. Non-coding RNAs: Meet thy masters. Bioessays 2010; 32:599-608; PMID:20544733; http://dx.doi.org/10.1002/bies.200900112.
85. Mattick JS. The genetic signatures of noncod-ing RNAs. PLoS Genet 2009; 5:e1000459; PMID:19390609; http://dx.doi.org/10.1371/jour-nal.pgen.1000459.
86. Martin L, Chang HY. Uncovering the role of genom-ic "dark matter" in human disease. J Clin Invest 2012; 122:1589-95; PMID:22546862; http://dx.doi.org/10.1172/JCI60020.
87. Rastinejad F, Blau HM. Genetic complementation reveals a novel regulatory role for 3' untranslated regions in growth and differentiation. Cell 1993; 72:903-17; PMID:8384533; http://dx.doi.org/10.1016/0092-8674(93)90579-F.
88. Jupe ER, Liu XT, Kiehlbauch JL, McClung JK, Dell'Orco RT. Prohibitin in breast cancer cell lines: loss of antiproliferative activity is linked to 3' untranslated region mutations. Cell Growth Differ 1996; 7:871-8; PMID:8809404.
89. Fan XC, Steitz JA. Overexpression of HuR, a nucle-ar-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs. EMBO J 1998; 17:3448-60; PMID:9628880; http://dx.doi.org/10.1093/emboj/17.12.3448.
90. Amack JD, Paguio AP, Mahadevan MS. Cis and trans effects of the myotonic dystrophy (DM) mutation in a cell culture model. Hum Mol Genet 1999; 8:1975-84; PMID:10484765; http://dx.doi.org/10.1093/hmg/8.11.1975.
91. Jenny A, Hachet O, Závorszky P, Cyrklaff A, Weston MD, Johnston DS, et al. A translation-independent role of oskar RNA in early Drosophila oogenesis. Development 2006; 133:2827-33; PMID:16835436; http://dx.doi.org/10. 1242/dev.02456.
92. Candeias MM, Malbert-Colas L, Powell DJ, Daskalogianni C, Maslon MM, Naski N, et al. P53 mRNA controls p53 activity by managing Mdm2 functions. Nat Cell Biol 2008; 10:1098-105; PMID:19160491; http://dx.doi.org/10.1038/nc b17 70.
93. Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 2010; 465:1033-8; PMID:20577206; http://dx.doi.org/10.1038/ nature09144.
94. Kondo T, Plaza S, Zanet J, Benrabah E, Valenti P, Hashimoto Y, et al. Small peptides switch the transcriptional activity of Shavenbaby during Drosophila embryogenesis. Science 2010; 329:336-9; PMID:20647469; http://dx.doi.org/10.1126/sci-enc e.118 8158.