1932

Abstract

Short interspersed nuclear elements (SINEs) are nonautonomous retrotransposons that occupy approximately 13% of the human genome. They are transcribed by RNA polymerase III and can be retrotranscribed and inserted back into the genome with the help of other autonomous retroelements. Because they are preferentially located close to or within gene-rich regions, they can regulate gene expression by various mechanisms that act at both the DNA and the RNA levels. In this review, we summarize recent findings on the involvement of SINEs in different types of gene regulation and discuss the potential regulatory functions of SINEs that are in close proximity to genes, Pol III–transcribed SINE RNAs, and embedded SINE sequences within Pol II–transcribed genes in the human genome. These discoveries illustrate how the human genome has exapted some SINEs into functional regulatory elements.

Keyword(s): Alugene regulationIRAluMIRSINE
Loading

Article metrics loading...

/content/journals/10.1146/annurev-genom-111620-100736
2021-08-31
2024-10-15
Loading full text...

Full text loading...

/deliver/fulltext/genom/22/1/annurev-genom-111620-100736.html?itemId=/content/journals/10.1146/annurev-genom-111620-100736&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Abrusán G, Krambeck H-J. 2006. The distribution of L1 and Alu retroelements in relation to GC content on human sex chromosomes is consistent with the ectopic recombination model. J. Mol. Evol. 63:484–92
    [Google Scholar]
  2. 2. 
    Ahl V, Keller H, Schmidt S, Weichenrieder O. 2015. Retrotransposition and crystal structure of an Alu RNP in the ribosome-stalling conformation. Mol. Cell 60:715–27
    [Google Scholar]
  3. 3. 
    Ahmad S, Mu X, Yang F, Greenwald E, Park JW et al. 2018. Breaching self-tolerance to Alu duplex RNA underlies MDA5-mediated inflammation. Cell 172:797–810.e13
    [Google Scholar]
  4. 4. 
    Aird D, Teng T, Huang CL, Pazolli E, Banka D et al. 2019. Sensitivity to splicing modulation of BCL2 family genes defines cancer therapeutic strategies for splicing modulators. Nat. Commun. 10:137
    [Google Scholar]
  5. 5. 
    Akopian D, Shen K, Zhang X, Shan S-O. 2013. Signal recognition particle: an essential protein-targeting machine. Annu. Rev. Biochem. 82:693–721
    [Google Scholar]
  6. 6. 
    Aktaş T, Avşar Ilık İ, Maticzka D, Bhardwaj V, Pessoa Rodrigues C et al. 2017. DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome. Nature 544:115–19
    [Google Scholar]
  7. 7. 
    Ambati J, Fowler BJ. 2012. Mechanisms of age-related macular degeneration. Neuron 75:26–39
    [Google Scholar]
  8. 8. 
    Athanasiadis A, Rich A, Maas S. 2004. Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome. PLOS Biol 2:e391
    [Google Scholar]
  9. 9. 
    Babich V, Aksenov N, Alexeenko V, Oei SL, Buchlow G, Tomilin N. 1999. Association of some potential hormone response elements in human genes with the Alu family repeats. Gene 239:341–49
    [Google Scholar]
  10. 10. 
    Batut P, Dobin A, Plessy C, Carninci P, Gingeras TR. 2013. High-fidelity promoter profiling reveals widespread alternative promoter usage and transposon-driven developmental gene expression. Genome Res 23:169–80
    [Google Scholar]
  11. 11. 
    Batut P, Gingeras TR. 2013. RAMPAGE: promoter activity profiling by paired-end sequencing of 5′-complete cDNAs. Curr. Protoc. Mol. Biol. 104:25B.11.1–16
    [Google Scholar]
  12. 12. 
    Ben-Asouli Y, Banai Y, Pel-Or Y, Shir A, Kaempfer R 2002. Human interferon-γ mRNA autoregulates its translation through a pseudoknot that activates the interferon-inducible protein kinase PKR. Cell 108:221–32
    [Google Scholar]
  13. 13. 
    Berger A, Ivanova E, Gareau C, Scherrer A, Mazroui R, Strub K. 2014. Direct binding of the Alu binding protein dimer SRP9/14 to 40S ribosomal subunits promotes stress granule formation and is regulated by Alu RNA. Nucleic Acids Res 42:11203–17
    [Google Scholar]
  14. 14. 
    Bovia F, Wolff N, Ryser S, Strub K. 1997. The SRP9/14 subunit of the human signal recognition particle binds to a variety of Alu-like RNAs and with higher affinity than its mouse homolog. Nucleic Acids Res 25:318–26
    [Google Scholar]
  15. 15. 
    Bowling EA, Wang JH, Gong F, Wu W, Neill NJ et al. 2021. Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer. Cell 184:384–403.e21
    [Google Scholar]
  16. 16. 
    Brocks D, Schmidt CR, Daskalakis M, Jang HS, Shah NM et al. 2017. DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats. Nat. Genet. 49:1052–60
    [Google Scholar]
  17. 17. 
    Cao Y, Chen G, Wu G, Zhang X, McDermott J et al. 2019. Widespread roles of enhancer-like transposable elements in cell identity and long-range genomic interactions. Genome Res 29:40–52
    [Google Scholar]
  18. 18. 
    Capel B, Swain A, Nicolis S, Hacker A, Walter M et al. 1993. Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell 73:1019–30
    [Google Scholar]
  19. 19. 
    Carnevali D, Conti A, Pellegrini M, Dieci G. 2017. Whole-genome expression analysis of mammalian-wide interspersed repeat elements in human cell lines. DNA Res 24:59–69
    [Google Scholar]
  20. 20. 
    Chang DY, Hsu K, Maraia RJ. 1996. Monomeric scAlu and nascent dimeric Alu RNAs induced by adenovirus are assembled into SRP9/14-containing RNPs in HeLa cells. Nucleic Acids Res 24:4165–70
    [Google Scholar]
  21. 21. 
    Chen L-L. 2020. The expanding regulatory mechanisms and cellular functions of circular RNAs. Nat. Rev. Mol. Cell Biol. 21:475–90
    [Google Scholar]
  22. 22. 
    Chen L-L, Carmichael GG. 2009. Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: functional role of a nuclear noncoding RNA. Mol. Cell 35:467–78
    [Google Scholar]
  23. 23. 
    Chen L-L, DeCerbo JN, Carmichael GG. 2008. Alu element-mediated gene silencing. EMBO J 27:1694–705
    [Google Scholar]
  24. 24. 
    Chiappinelli KB, Strissel PL, Desrichard A, Li H, Henke C et al. 2015. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162:974–86
    [Google Scholar]
  25. 25. 
    Chillón I, Pyle AM. 2016. Inverted repeat Alu elements in the human lincRNA-p21 adopt a conserved secondary structure that regulates RNA function. Nucleic Acids Res 44:9462–71
    [Google Scholar]
  26. 26. 
    Chishima T, Iwakiri J, Hamada M. 2018. Identification of transposable elements contributing to tissue-specific expression of long non-coding RNAs. Genes 9:23
    [Google Scholar]
  27. 27. 
    Chung H, Calis JJA, Wu X, Sun T, Yu Y et al. 2018. Human ADAR1 prevents endogenous RNA from triggering translational shutdown. Cell 172:811–24.e14
    [Google Scholar]
  28. 28. 
    Chuong EB, Elde NC, Feschotte C. 2017. Regulatory activities of transposable elements: from conflicts to benefits. Nat. Rev. Genet. 18:71–86
    [Google Scholar]
  29. 29. 
    Conti A, Carnevali D, Bollati V, Fustinoni S, Pellegrini M, Dieci G. 2015. Identification of RNA polymerase III-transcribed Alu loci by computational screening of RNA-Seq data. Nucleic Acids Res 43:817–35
    [Google Scholar]
  30. 30. 
    Deininger PL. 2011. Alu elements: know the SINEs. Genome Biol 12:236
    [Google Scholar]
  31. 31. 
    Deininger PL, Schmid CW. 1976. An electron microscope study of the DNA sequence organization of the human genome. J. Mol. Biol. 106:773–90
    [Google Scholar]
  32. 32. 
    del Toro Duany Y, Wu B, Hur S. 2015. MDA5—filament, dynamics and disease. Curr. Opin. Virol. 12:20–25
    [Google Scholar]
  33. 33. 
    Dong R, Ma X-K, Chen L-L, Yang L 2017. Increased complexity of circRNA expression during species evolution. RNA Biol 14:1064–74
    [Google Scholar]
  34. 34. 
    Dubin RA, Kazmi MA, Ostrer H. 1995. Inverted repeats are necessary for circularization of the mouse testis Sry transcript. Gene 167:245–48
    [Google Scholar]
  35. 35. 
    Elbarbary RA, Li W, Tian B, Maquat LE. 2013. STAU1 binding 3′ UTR IRAlus complements nuclear retention to protect cells from PKR-mediated translational shutdown. Genes Dev 27:1495–510
    [Google Scholar]
  36. 36. 
    Elbarbary RA, Maquat LE. 2017. Distinct mechanisms obviate the potentially toxic effects of inverted-repeat Alu elements on cellular RNA metabolism. Nat. Struct. Mol. Biol. 24:496–98
    [Google Scholar]
  37. 37. 
    Eller CD, Regelson M, Merriman B, Nelson S, Horvath S, Marahrens Y. 2007. Repetitive sequence environment distinguishes housekeeping genes. Gene 390:153–65
    [Google Scholar]
  38. 38. 
    ENCODE Proj. Consort., Moore JE, Purcaro MJ, Pratt HE, Epstein CB et al. 2020. Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature 583:699–710
    [Google Scholar]
  39. 39. 
    Faulkner GJ, Kimura Y, Daub CO, Wani S, Plessy C et al. 2009. The regulated retrotransposon transcriptome of mammalian cells. Nat. Genet. 41:563–71
    [Google Scholar]
  40. 40. 
    Ferrari R, de Llobet Cucalon LI, Di Vona C, Le Dilly F, Vidal E et al. 2020. TFIIIC binding to Alu elements controls gene expression via chromatin looping and histone acetylation. Mol. Cell 77:475–87.e11
    [Google Scholar]
  41. 41. 
    Fox AH, Nakagawa S, Hirose T, Bond CS. 2018. Paraspeckles: where long noncoding RNA meets phase separation. Trends Biochem. Sci. 43:124–35
    [Google Scholar]
  42. 42. 
    Frankish A, Diekhans M, Ferreira A-M, Johnson R, Jungreis I et al. 2019. GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res 47:D766–73
    [Google Scholar]
  43. 43. 
    Gong C, Maquat LE. 2011. lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements. Nature 470:284–88
    [Google Scholar]
  44. 44. 
    Gong C, Tang Y, Maquat LE. 2013. mRNA–mRNA duplexes that autoelicit Staufen1-mediated mRNA decay. Nat. Struct. Mol. Biol. 20:1214–20
    [Google Scholar]
  45. 45. 
    Goodall GJ, Wickramasinghe VO. 2020. RNA in cancer. Nat. Rev. Cancer 21:22–36
    [Google Scholar]
  46. 46. 
    Grover D, Majumder PP, Rao CB, Brahmachari SK, Mukerji M. 2003. Nonrandom distribution of Alu elements in genes of various functional categories: insight from analysis of human chromosomes 21 and 22. Mol. Biol. Evol. 20:1420–24
    [Google Scholar]
  47. 47. 
    Grover D, Mukerji M, Bhatnagar P, Kannan K, Brahmachari SK. 2004. Alu repeat analysis in the complete human genome: trends and variations with respect to genomic composition. Bioinformatics 20:813–17
    [Google Scholar]
  48. 48. 
    Guo C-J, Xu G, Chen L-L. 2020. Mechanisms of long noncoding RNA nuclear retention. Trends Biochem. Sci. 45:947–60
    [Google Scholar]
  49. 49. 
    Han T, Goralski M, Gaskill N, Capota E, Kim J et al. 2017. Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science 356:eaal3755
    [Google Scholar]
  50. 50. 
    Häsler J, Strub K. 2006. Alu RNP and Alu RNA regulate translation initiation in vitro. Nucleic Acids Res 34:2374–85
    [Google Scholar]
  51. 51. 
    Hsu TYT, Simon LM, Neill NJ, Marcotte R, Sayad A et al. 2015. The spliceosome is a therapeutic vulnerability in MYC-driven cancer. Nature 525:384–88
    [Google Scholar]
  52. 52. 
    Hu S-B, Xiang J-F, Li X, Xu Y, Xue W et al. 2015. Protein arginine methyltransferase CARM1 attenuates the paraspeckle-mediated nuclear retention of mRNAs containing IRAlus. Genes Dev 29:630–45
    [Google Scholar]
  53. 53. 
    Hubert CG, Bradley RK, Ding Y, Toledo CM, Herman J et al. 2013. Genome-wide RNAi screens in human brain tumor isolates reveal a novel viability requirement for PHF5A. Genes Dev 27:1032–45
    [Google Scholar]
  54. 54. 
    Hur S. 2019. Double-stranded RNA sensors and modulators in innate immunity. Annu. Rev. Immunol. 37:349–75
    [Google Scholar]
  55. 55. 
    Ivanov A, Memczak S, Wyler E, Torti F, Porath HT et al. 2015. Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep 10:170–77
    [Google Scholar]
  56. 56. 
    Ivanova E, Berger A, Scherrer A, Alkalaeva E, Strub K. 2015. Alu RNA regulates the cellular pool of active ribosomes by targeted delivery of SRP9/14 to 40S subunits. Nucleic Acids Res 43:2874–87
    [Google Scholar]
  57. 57. 
    Jackson RJ, Hellen CUT, Pestova TV. 2010. The mechanism of eukaryotic translation initiation and principles of its regulation. Nat. Rev. Mol. Cell Biol. 11:113–27
    [Google Scholar]
  58. 58. 
    Jang HS, Shah NM, Du AY, Dailey ZZ, Pehrsson EC et al. 2019. Transposable elements drive widespread expression of oncogenes in human cancers. Nat. Genet. 51:611–17
    [Google Scholar]
  59. 59. 
    Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE et al. 2013. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 19:141–57
    [Google Scholar]
  60. 60. 
    Jordà M, Díez-Villanueva A, Mallona I, Martín B, Lois S et al. 2017. The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells. Genome Res 27:118–32
    [Google Scholar]
  61. 61. 
    Jordan IK, Rogozin IB, Glazko GV, Koonin EV. 2003. Origin of a substantial fraction of human regulatory sequences from transposable elements. Trends Genet 19:68–72
    [Google Scholar]
  62. 62. 
    Jurka J, Kohany O, Pavlicek A, Kapitonov VV, Jurka MV 2004. Duplication, coclustering, and selection of human Alu retrotransposons. PNAS 101:1268–72
    [Google Scholar]
  63. 63. 
    Kaneko H, Dridi S, Tarallo V, Gelfand BD, Fowler BJ et al. 2011. DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. Nature 471:325–30
    [Google Scholar]
  64. 64. 
    Kapusta A, Kronenberg Z, Lynch VJ, Zhuo X, Ramsay L et al. 2013. Transposable elements are major contributors to the origin, diversification, and regulation of vertebrate long noncoding RNAs. PLOS Genet 9:e1003470
    [Google Scholar]
  65. 65. 
    Kim DDY, Kim TTY, Walsh T, Kobayashi Y, Matise TC et al. 2004. Widespread RNA editing of embedded Alu elements in the human transcriptome. Genome Res 14:1719–25
    [Google Scholar]
  66. 66. 
    Kim S, Ku Y, Ku J, Kim Y. 2019. Evidence of aberrant immune response by endogenous double-stranded RNAs: attack from within. BioEssays 41:e1900023
    [Google Scholar]
  67. 67. 
    Kim Y, Lee JH, Park J-E, Cho J, Yi H, Kim VN 2014. PKR is activated by cellular dsRNAs during mitosis and acts as a mitotic regulator. Genes Dev 28:1310–22
    [Google Scholar]
  68. 68. 
    Kim Y, Park J, Kim S, Kim M, Kang M-G et al. 2018. PKR senses nuclear and mitochondrial signals by interacting with endogenous double-stranded RNAs. Mol. Cell 71:1051–63.e6
    [Google Scholar]
  69. 69. 
    Konkel MK, Walker JA, Hotard AB, Ranck MC, Fontenot CC et al. 2015. Sequence analysis and characterization of active human Alu subfamilies based on the 1000 Genomes pilot project. Genome Biol. Evol. 7:2608–22
    [Google Scholar]
  70. 70. 
    Korenberg JR, Rykowski MC. 1988. Human genome organization: Alu, LINES, and the molecular structure of metaphase chromosome bands. Cell 53:391–400
    [Google Scholar]
  71. 71. 
    Lagisetti C, Palacios G, Goronga T, Freeman B, Caufield W et al. 2013. Optimization of antitumor modulators of pre-mRNA splicing. J. Med. Chem. 56:10033–44
    [Google Scholar]
  72. 72. 
    Lakkaraju AKK, Mary C, Scherrer A, Johnson AE, Strub K. 2008. SRP keeps polypeptides translocation-competent by slowing translation to match limiting ER-targeting sites. Cell 133:440–51
    [Google Scholar]
  73. 73. 
    Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC et al. 2001. Initial sequencing and analysis of the human genome. Nature 409:860–921
    [Google Scholar]
  74. 74. 
    Laperriere D, Wang T-T, White JH, Mader S. 2007. Widespread Alu repeat-driven expansion of consensus DR2 retinoic acid response elements during primate evolution. BMC Genom 8:23
    [Google Scholar]
  75. 75. 
    Li X, Liu C-X, Xue W, Zhang Y, Jiang S et al. 2017. Coordinated circRNA biogenesis and function with NF90/NF110 in viral infection. Mol. Cell 67:214–27.e7
    [Google Scholar]
  76. 76. 
    Liang D, Wilusz JE. 2014. Short intronic repeat sequences facilitate circular RNA production. Genes Dev 28:2233–47
    [Google Scholar]
  77. 77. 
    Liddicoat BJ, Piskol R, Chalk AM, Ramaswami G, Higuchi M et al. 2015. RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself. Science 349:1115–20
    [Google Scholar]
  78. 78. 
    Lubelsky Y, Ulitsky I. 2018. Sequences enriched in Alu repeats drive nuclear localization of long RNAs in human cells. Nature 555:107–11
    [Google Scholar]
  79. 79. 
    Mao YS, Sunwoo H, Zhang B, Spector DL. 2011. Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding RNAs. Nat. Cell Biol. 13:95–101
    [Google Scholar]
  80. 80. 
    Mariner PD, Walters RD, Espinoza CA, Drullinger LF, Wagner SD et al. 2008. Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Mol. Cell 29:499–509
    [Google Scholar]
  81. 81. 
    McHaffie GS, Ralston SH. 1995. Origin of a negative calcium response element in an ALU-repeat: implications for regulation of gene expression by extracellular calcium. Bone 17:11–14
    [Google Scholar]
  82. 82. 
    Mehdipour P, Marhon SA, Ettayebi I, Chakravarthy A, Hosseini A et al. 2020. Epigenetic therapy induces transcription of inverted SINEs and ADAR1 dependency. Nature 588:169–73
    [Google Scholar]
  83. 83. 
    Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J et al. 2013. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495:333–38
    [Google Scholar]
  84. 84. 
    Mills RE, Andrew Bennett E, Iskow RC, Devine SE 2007. Which transposable elements are active in the human genome?. Trends Genet. 23:183–91
    [Google Scholar]
  85. 85. 
    Moqtaderi Z, Wang J, Raha D, White RJ, Snyder M et al. 2010. Genomic binding profiles of functionally distinct RNA polymerase III transcription complexes in human cells. Nat. Struct. Mol. Biol. 17:635–40
    [Google Scholar]
  86. 86. 
    Moyzis RK, Torney DC, Meyne J, Buckingham JM, Wu JR et al. 1989. The distribution of interspersed repetitive DNA sequences in the human genome. Genomics 4:273–89
    [Google Scholar]
  87. 87. 
    Oler AJ, Alla RK, Roberts DN, Wong A, Hollenhorst PC et al. 2010. Human RNA polymerase III transcriptomes and relationships to Pol II promoter chromatin and enhancer-binding factors. Nat. Struct. Mol. Biol. 17:620–28
    [Google Scholar]
  88. 88. 
    Orioli A, Pascali C, Pagano A, Teichmann M, Dieci G. 2012. RNA polymerase III transcription control elements: themes and variations. Gene 493:185–94
    [Google Scholar]
  89. 89. 
    Ottesen EW, Luo D, Seo J, Singh NN, Singh RN. 2019. Human Survival Motor Neuron genes generate a vast repertoire of circular RNAs. Nucleic Acids Res 47:2884–905
    [Google Scholar]
  90. 90. 
    Panning B, Smiley JR. 1995. Activation of expression of multiple subfamilies of human Alu elements by adenovirus type 5 and herpes simplex virus type 1. J. Mol. Biol. 248:513–24
    [Google Scholar]
  91. 91. 
    Paolella G, Lucero MA, Murphy MH, Baralle FE. 1983. The Alu family repeat promoter has a tRNA-like bipartite structure. EMBO J 2:691–96
    [Google Scholar]
  92. 92. 
    Park E, Maquat LE. 2013. Staufen-mediated mRNA decay. WIREs RNA 4:423–35
    [Google Scholar]
  93. 93. 
    Pasquesi GIM, Perry BW, Vandewege MW, Ruggiero RP, Schield DR, Castoe TA. 2020. Vertebrate lineages exhibit diverse patterns of transposable element regulation and expression across tissues. Genome Biol. Evol. 12:506–21
    [Google Scholar]
  94. 94. 
    Patiño C, Haenni A-L, Urcuqui-Inchima S. 2015. NF90 isoforms, a new family of cellular proteins involved in viral replication?. Biochimie 108:20–24
    [Google Scholar]
  95. 95. 
    Paulson KE, Schmid CW. 1986. Transcriptional inactivity of Alu repeats in HeLa cells. Nucleic Acids Res 14:6145–58
    [Google Scholar]
  96. 96. 
    Pestal K, Funk CC, Snyder JM, Price ND, Treuting PM, Stetson DB. 2015. Isoforms of RNA-editing enzyme ADAR1 independently control nucleic acid sensor MDA5-driven autoimmunity and multi-organ development. Immunity 43:933–44
    [Google Scholar]
  97. 97. 
    Pham AM, Santa Maria FG, Lahiri T, Friedman E, Marié IJ, Levy DE 2016. PKR transduces MDA5-dependent signals for type I IFN induction. PLOS Pathog 12:e1005489
    [Google Scholar]
  98. 98. 
    Polak P, Domany E. 2006. Alu elements contain many binding sites for transcription factors and may play a role in regulation of developmental processes. BMC Genom 7:133
    [Google Scholar]
  99. 99. 
    Rice GI, Kasher PR, Forte GMA, Mannion NM, Greenwood SM et al. 2012. Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature. Nat. Genet. 44:1243–48
    [Google Scholar]
  100. 100. 
    Romanish MT, Nakamura H, Lai CB, Wang Y, Mager DL. 2009. A novel protein isoform of the multicopy human NAIP gene derives from intragenic Alu SINE promoters. PLOS ONE 4:e5761
    [Google Scholar]
  101. 101. 
    Roulois D, Yau HL, Singhania R, Wang Y, Danesh A et al. 2015. DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell 162:961–73
    [Google Scholar]
  102. 102. 
    Rybak-Wolf A, Stottmeister C, Glažar P, Jens M, Pino N et al. 2015. Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Mol. Cell 58:870–85
    [Google Scholar]
  103. 103. 
    Sasaki YTF, Ideue T, Sano M, Mituyama T, Hirose T 2009. MENε/β noncoding RNAs are essential for structural integrity of nuclear paraspeckles. PNAS 106:2525–30
    [Google Scholar]
  104. 104. 
    Schmid CW, Deininger PL. 1975. Sequence organization of the human genome. Cell 6:345–58
    [Google Scholar]
  105. 105. 
    Seiler M, Yoshimi A, Darman R, Chan B, Keaney G et al. 2018. H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers. Nat. Med. 24:497–504
    [Google Scholar]
  106. 106. 
    Sharma P, Siwen H, Jennifer W, Antoni R 2017. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 168:707–23
    [Google Scholar]
  107. 107. 
    Sinnett D, Richer C, Deragon JM, Labuda D. 1991. Alu RNA secondary structure consists of two independent 7 SL RNA-like folding units. J. Biol. Chem. 266:8675–78
    [Google Scholar]
  108. 108. 
    Smit AF, Riggs AD. 1995. MIRs are classic, tRNA-derived SINEs that amplified before the mammalian radiation. Nucleic Acids Res 23:98–102
    [Google Scholar]
  109. 109. 
    Song M-S, Rossi JJ. 2017. Molecular mechanisms of Dicer: endonuclease and enzymatic activity. Biochem. J. 474:1603–18
    [Google Scholar]
  110. 110. 
    Su M, Han D, Boyd-Kirkup J, Yu X, Han J-DJ 2014. Evolution of Alu elements toward enhancers. Cell Rep 7:376–85
    [Google Scholar]
  111. 111. 
    Swanson KV, Deng M, Ting JP-Y. 2019. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat. Rev. Immunol. 19:477–89
    [Google Scholar]
  112. 112. 
    Tang R-B, Wang H-Y, Lu H-Y, Xiong J, Li H-H et al. 2005. Increased level of polymerase III transcribed Alu RNA in hepatocellular carcinoma tissue. Mol. Carcinog. 42:93–96
    [Google Scholar]
  113. 113. 
    Tarallo V, Hirano Y, Gelfand BD, Dridi S, Kerur N et al. 2012. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell 149:847–59
    [Google Scholar]
  114. 114. 
    Uehara T, Minoshima Y, Sagane K, Sugi NH, Mitsuhashi KO et al. 2017. Selective degradation of splicing factor CAPERα by anticancer sulfonamides. Nat. Chem. Biol. 13:675–80
    [Google Scholar]
  115. 115. 
    Van Bortle K, Corces VG. 2012. tDNA insulators and the emerging role of TFIIIC in genome organization. Transcription 3:277–84
    [Google Scholar]
  116. 116. 
    van de Lagemaat LN, Landry J-R, Mager DL, Medstrand P. 2003. Transposable elements in mammals promote regulatory variation and diversification of genes with specialized functions. Trends Genet 19:530–36
    [Google Scholar]
  117. 117. 
    Vansant G, Reynolds WF 1995. The consensus sequence of a major Alu subfamily contains a functional retinoic acid response element. PNAS 92:8229–33
    [Google Scholar]
  118. 118. 
    Varshney D, Vavrova-Anderson J, Oler AJ, Cowling VH, Cairns BR, White RJ. 2015. SINE transcription by RNA polymerase III is suppressed by histone methylation but not by DNA methylation. Nat. Commun. 6:6569
    [Google Scholar]
  119. 119. 
    Wang J, Vicente-García C, Seruggia D, Moltó E, Fernandez-Miñán A et al. 2015. MIR retrotransposon sequences provide insulators to the human genome. PNAS 112:E4428–37
    [Google Scholar]
  120. 120. 
    Wu G, Cai J, Han Y, Chen J, Huang Z-P et al. 2014. LincRNA-p21 regulates neointima formation, vascular smooth muscle cell proliferation, apoptosis, and atherosclerosis by enhancing p53 activity. Circulation 130:1452–65
    [Google Scholar]
  121. 121. 
    Yang F, Zhang H, Mei Y, Wu M. 2014. Reciprocal regulation of HIF-1α and lincRNA-p21 modulates the Warburg effect. Mol. Cell 53:88–100
    [Google Scholar]
  122. 122. 
    Yoon J-H, Abdelmohsen K, Srikantan S, Yang X, Martindale JL et al. 2012. LincRNA-p21 suppresses target mRNA translation. Mol. Cell 47:648–55
    [Google Scholar]
  123. 123. 
    Żemojtel T, Kiełbasa SM, Arndt PF, Behrens S, Bourque G, Vingron M. 2011. CpG deamination creates transcription factor-binding sites with high efficiency. Genome Biol. Evol. 3:1304–11
    [Google Scholar]
  124. 124. 
    Zemojtel T, Kielbasa SM, Arndt PF, Chung H-R, Vingron M. 2009. Methylation and deamination of CpGs generate p53-binding sites on a genomic scale. Trends Genet 25:63–66
    [Google Scholar]
  125. 125. 
    Zhang L, Chen J-G, Zhao Q. 2015. Regulatory roles of Alu transcript on gene expression. Exp. Cell Res. 338:113–18
    [Google Scholar]
  126. 126. 
    Zhang P, Zhang X-O, Jiang T, Cai L, Huang X et al. 2020. Comprehensive identification of alternative back-splicing in human tissue transcriptomes. Nucleic Acids Res 48:1779–89
    [Google Scholar]
  127. 127. 
    Zhang X-O, Dong R, Zhang Y, Zhang J-L, Luo Z et al. 2016. Diverse alternative back-splicing and alternative splicing landscape of circular RNAs. Genome Res 26:1277–87
    [Google Scholar]
  128. 128. 
    Zhang X-O, Gingeras TR, Weng Z. 2019. Genome-wide analysis of polymerase III-transcribed elements suggests cell-type-specific enhancer function. Genome Res 29:1402–14
    [Google Scholar]
  129. 129. 
    Zhang X-O, Wang H-B, Zhang Y, Lu X, Chen L-L, Yang L 2014. Complementary sequence-mediated exon circularization. Cell 159:134–47
    [Google Scholar]
/content/journals/10.1146/annurev-genom-111620-100736
Loading
/content/journals/10.1146/annurev-genom-111620-100736
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error