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Long Noncoding RNAs and Their Applications: Focus on Architectural RNA (arcRNA), a Class of lncRNA

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Applied RNA Bioscience

Abstract

Transcriptome analyses have revealed large numbers of non-protein coding transcripts called noncoding RNAs (ncRNAs), which are produced from most genomic regions in mammalian cells. These ncRNAs include many thousands of long noncoding RNAs (lncRNAs) more than 200 nucleotides in length. Although our knowledge of these lncRNAs remains limited, recent studies have revealed their diverse roles under physiological and pathological conditions, as well as their mechanisms of action in a variety of cellular processes including epigenetic regulation, transcriptional regulation, posttranscriptional processing, and intracellular organization. In addition, multiple studies show that aberrant expression of lncRNAs is associated with various diseases, including cancer and neurodegenerative disorders, suggesting that lncRNAs represent promising target molecules for biomedical applications. Here, I review lncRNAs and several related applications and in particular an emerging class of lncRNAs termed architectural RNA (arcRNA). I describe and discuss arcRNAs in mammals, focusing on their biogenesis, mechanisms of action, and potential applications. In addition, I highlight our newly established methods for discovering arcRNA candidates. Finally, I emphasize the importance of identifying the RNA elements embedded in lncRNAs that dictate their functions; these elements provide opportunities for future applications in biotechnology, biomarkers, and therapeutics.

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References

  • Adriaens C, Standaert L, Barra J, Latil M, Verfaillie A, Kalev P, Boeckx B, Wijnhoven PW, Radaelli E, Vermi W, Leucci E, Lapouge G, Beck B, van den Oord J, Nakagawa S, Hirose T, Sablina AA, Lambrechts D, Aerts S, Blanpain C, Marine JC (2016) p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity. Nat Med 22:861–868

    Article  CAS  PubMed  Google Scholar 

  • Aguzzi A, Altmeyer M (2016) Phase separation: linking cellular compartmentalization to disease. Trends Cell Biol 26:547–558

    Article  CAS  PubMed  Google Scholar 

  • Alberti S, Hyman AA (2016) Are aberrant phase transitions a driver of cellular aging? BioEssays 38:959–968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anderson DM, Anderson KM, Chang CL, Makarewich CA, Nelson BR, McAnally JR, Kasaragod P, Shelton JM, Liou J, Bassel-Duby R, Olson EN (2015) A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell 160:595–606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, Evantal N, Memczak S, Rajewsky N, Kadener S (2014) circRNA biogenesis competes with pre-mRNA splicing. Mol Cell 56:55–66

    Article  CAS  PubMed  Google Scholar 

  • Audas TE, Jacob MD, Lee S (2012a) Immobilization of proteins in the nucleolus by ribosomal intergenic spacer noncoding RNA. Mol Cell 45:147–517

    Article  CAS  PubMed  Google Scholar 

  • Audas TE, Jacob MD, Lee S (2012b) The nucleolar detention pathway: a cellular strategy for regulating molecular networks. Cell Cycle 11:2059–2062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Audas TE, Audas DE, Jacob MD, Ho JJ, Khacho M, Wang M, Perera JK, Gardiner C, Bennett CA, Head T, Kryvenko ON, Jorda M, Daunert S, Malhotra A, Trinkle-Mulcahy L, Gonzalgo ML, Lee S (2016) Adaptation to stressors by systemic protein amyloidogenesis. Dev Cell 39:155–168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baltz AG, Munschauer M, Schwanhäusser B, Vasile A, Murakawa Y, Schueler M, Youngs N, Penfold-Brown D, Drew K, Milek M, Wyler E, Bonneau R, Selbach M, Dieterich C, Landthaler M (2012) The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Mol Cell 46:674–690

    Article  CAS  PubMed  Google Scholar 

  • Banani SF, Lee HO, Hyman AA, Rosen MK (2017) Biomolecular condensates: organizers of cellular biochemistry. Nat Rev Mol Cell Biol 18:285–298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barry G, Briggs JA, Hwang DW, Nayler SP, Fortuna PR, Jonkhout N, Dachet F, Maag JL, Mestdagh P, Singh EM, Avesson L, Kaczorowski DC, Ozturk E, Jones NC, Vetter I, Arriola-Martinez L, Hu J, Franco GR, Warn VM, Gong A, Dinger ME, Rigo F, Lipovich L, Morris MJ, O'Brien TJ, Lee DS, Loeb JA, Blackshaw S, Mattick JS, Wolvetang EJ (2017) The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states. Sci Rep 7:40127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Belzil VV, Gendron TF, Petrucelli L (2013) RNA-mediated toxicity in neurodegenerative disease. Mol Cell Neurosci 56:406–419

    Article  CAS  PubMed  Google Scholar 

  • Bertone P, Stolc V, Royce TE, Rozowsky JS, Urban AE, Zhu X, Rinn JL, Tongprasit W, Samanta M, Weissman S, Gerstein M, Snyder M (2004) Global identification of human transcribed sequences with genome tiling arrays. Science 306:2242–2246

    Article  CAS  PubMed  Google Scholar 

  • Biamonti G (2004) Nuclear stress bodies: a heterochromatin affair? Nat Rev Mol Cell Biol 5:493–498

    Article  CAS  PubMed  Google Scholar 

  • Biamonti G, Vourc’h C (2010) Nuclear stress bodies. Cold Spring Harb Perspect Biol 2:a000695

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Blume CJ, Hotz-Wagenblatt A, Hüllein J, Sellner L, Jethwa A, Stolz T, Slabicki M, Lee K, Sharathchandra A, Benner A, Dietrich S, Oakes CC, Dreger P, te Raa D, Kater AP, Jauch A, Merkel O, Oren M, Hielscher T, Zenz T (2015) p53-dependent non-coding RNA networks in chronic lymphocytic leukemia. Leukemia 29:2015–2023

    Article  CAS  PubMed  Google Scholar 

  • Brown JA, Valenstein ML, Yario TA, Tycowski KT, Steitz JA (2012) Formation of triple-helical structures by the 3′-end sequences of MALAT1 and MENβ noncoding RNAs. Proc Natl Acad Sci U S A 109:19202–19207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schönbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y, FANTOM Consortium, RIKEN Genome Exploration Research Group, GenomeScience Group (Genome Network Project Core Group) (2005) The transcriptional landscape of the mammalian genome. Science 309:1559–1563

    Article  CAS  PubMed  Google Scholar 

  • Carrieri C, Cimatti L, Biagioli M, Beugnet A, Zucchelli S, Fedele S, Pesce E, Ferrer I, Collavin L, Santoro C, Forrest AR, Carninci P, Biffo S, Stupka E, Gustincich S (2012) Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature 491:454–457

    Article  CAS  PubMed  Google Scholar 

  • Castello A, Fischer B, Eichelbaum K, Horos R, Beckmann BM, Strein C, Davey NE, Humphreys DT, Preiss T, Steinmetz LM, Krijgsveld J, Hentze MW (2012) Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 149:1393–1406

    Article  CAS  PubMed  Google Scholar 

  • Castello A, Fischer B, Frese CK, Horos R, Alleaume AM, Foehr S, Curk T, Krijgsveld J, Hentze MW (2016) Comprehensive identification of RNA-binding domains in human cells. Mol Cell 63:696–710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cech TR, Steitz JA (2014) The noncoding RNA revolution-trashing old rules to forge new ones. Cell 157:77–94

    Article  CAS  PubMed  Google Scholar 

  • Chakravarty D, Sboner A, Nair SS, Giannopoulou E, Li R, Hennig S, Mosquera JM, Pauwels J, Park K, Kossai M, MacDonald TY, Fontugne J, Erho N, Vergara IA, Ghadessi M, Davicioni E, Jenkins RB, Palanisamy N, Chen Z, Nakagawa S, Hirose T, Bander NH, Beltran H, Fox AH, Elemento O, Rubin MA (2014) The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer. Nat Commun 5:5383

    Article  CAS  PubMed  Google Scholar 

  • Chen LL (2016a) The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol 17:205–211

    Article  CAS  PubMed  Google Scholar 

  • Chen LL (2016b) Linking long noncoding RNA localization and function. Trends Biochem Sci 41:761–772

    Article  CAS  PubMed  Google Scholar 

  • Chen LL, 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 35:467–478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen CK, Blanco M, Jackson C, Aznauryan E, Ollikainen N, Surka C, Chow A, Cerase A, McDonel P, Guttman M (2016) Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing. Science 354:468–472

    Article  CAS  PubMed  Google Scholar 

  • Chiodi I, Biggiogera M, Denegri M, Corioni M, Weighardt F, Cobianchi F, Riva S, Biamonti G (2000) Structure and dynamics of hnRNP-labelled nuclear bodies induced by stress treatments. J Cell Sci 113(Pt 22):4043–4053

    CAS  PubMed  Google Scholar 

  • Chiodi I, Corioni M, Giordano M, Valgardsdottir R, Ghigna C, Cobianchi F, Xu RM, Riva S, Biamonti G (2004) RNA recognition motif 2 directs the recruitment of SF2/ASF to nuclear stress bodies. Nucleic Acids Res 32:4127–4136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choo KH, Earle E, Mcquikkan C (1990) A homologous subfamily of satellite III DNA on human chromosomes 14 and 22. Nucleic Acids Res 18:5641–5648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choudhry H, Schödel J, Oikonomopoulos S, Camps C, Grampp S, Harris AL, Ratcliffe PJ, Ragoussis J, Mole DR (2014) Extensive regulation of the non-coding transcriptome by hypoxia: role of HIF in releasing paused RNApol2. EMBO Rep 15:70–76

    Article  CAS  PubMed  Google Scholar 

  • Choudhry H, Albukhari A, Morotti M, Haider S, Moralli D, Smythies J, Schödel J, Green CM, Camps C, Buffa F, Ratcliffe P, Ragoussis J, Harris AL, Mole DR (2015) Tumor hypoxia induces nuclear paraspeckle formation through HIF-2alpha dependent transcriptional activation of NEAT1 leading to cancer cell survival. Oncogene 34:4546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chu C, Zhang QC, da Rocha ST, Flynn RA, Bharadwaj M, Calabrese JM, Magnuson T, Heard E, Chang HY (2015) Systematic discovery of Xist RNA binding proteins. Cell 161:404–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chujo T, Yamazaki T, Hirose T (2016) Architectural RNAs (arcRNAs): a class of long noncoding RNAs that function as the scaffold of nuclear bodies. Biochim Biophys Acta 1859:139–146

    Article  CAS  PubMed  Google Scholar 

  • Chujo T, Yamazaki T, Kawaguchi T, Kurosaka S, Takumi T, Nakagawa S, Hirose T (2017) Unusual semi-extractability as a hallmark of nuclear body-associated architectural noncoding RNAs. EMBO J 36:1447–1462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clemson CM, Hutchinson JN, Sara SA, Ensminger AW, Fox AH, Chess A, Lawrence JB (2009) An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell 33:717–726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conrad NK, Steitz JA (2005) A Kaposi's sarcoma virus RNA element that increases the nuclear abundance of intronless transcripts. EMBO J 24:1831–1841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cotto J, Fox S, Morimoto R (1997) HSF1 granules: a novel stress-induced nuclear compartment of human cells. J Cell Sci 110(Pt 23):2925–2934

    CAS  PubMed  Google Scholar 

  • Courchaine EM, Lu A, Neugebauer KM (2016) Droplet organelles? EMBO J 35:1603–1612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Denegri M, Moralli D, Rocchi M, Biggiogera M, Raimondi E, Cobianchi F, De Carli L, Riva S, Biamonti G (2002) Human chromosomes 9, 12, and 15 contain the nucleation sites of stress-induced nuclear bodies. Mol Biol Cell 13:2069–2079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Engreitz JM, Haines JE, Perez EM, Munson G, Chen J, Kane M, McDonel PE, Guttman M, Lander ES (2016a) Local regulation of gene expression by lncRNA promoters, transcription and splicing. Nature 539:452–455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Engreitz JM, Ollikainen N, Guttman M (2016b) Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression. Nat Rev Mol Cell Biol 17:756–770

    Article  CAS  PubMed  Google Scholar 

  • Engström PG, Suzuki H, Ninomiya N, Akalin A, Sessa L, Lavorgna G, Brozzi A, Luzi L, Tan SL, Yang L, Kunarso G, Ng EL, Batalov S, Wahlestedt C, Kai C, Kawai J, Carninci P, Hayashizaki Y, Wells C, Bajic VB, Orlando V, Reid JF, Lenhard B, Lipovich L (2006) Complex Loci in human and mouse genomes. PLoS Genet 2:e47

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Enukashvily NI, Donev R, Waisertreiger IS, Podgornaya OI (2007) Human chromosome 1 satellite 3 DNA is decondensed, demethylated and transcribed in senescent cells and in A431 epithelial carcinoma cells. Cytogenet Genome Res 118:42–54

    Article  CAS  PubMed  Google Scholar 

  • Fong KW, Li Y, Wang W, Ma W, Li K, Qi RZ, Liu D, Songyang Z, Chen J (2013) Whole-genome screening identifies proteins localized to distinct nuclear bodies. J Cell Biol 203:149–164

    Article  PubMed  PubMed Central  Google Scholar 

  • Fox AH, Lam YW, Leung AK, Lyon CE, Andersen J, Mann M, Lamond AI (2002) Paraspeckles: a novel nuclear domain. Curr Biol 12:13–25

    Article  CAS  PubMed  Google Scholar 

  • Fujimoto A, Furuta M, Totoki Y, Tsunoda T, Kato M, Shiraishi Y, Tanaka H, Taniguchi H, Kawakami Y, Ueno M, Gotoh K, Ariizumi S, Wardell CP, Hayami S, Nakamura T, Aikata H, Arihiro K, Boroevich KA, Abe T, Nakano K, Maejima K, Sasaki-Oku A, Ohsawa A, Shibuya T, Nakamura H, Hama N, Hosoda F, Arai Y, Ohashi S, Urushidate T, Nagae G, Yamamoto S, Ueda H, Tatsuno K, Ojima H, Hiraoka N, Okusaka T, Kubo M, Marubashi S, Yamada T, Hirano S, Yamamoto M, Ohdan H, Shimada K, Ishikawa O, Yamaue H, Chayama K, Miyano S, Aburatani H, Shibata T, Nakagawa H (2016) Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer. Nat Genet 48:500–509

    Article  CAS  PubMed  Google Scholar 

  • Geisler S, Coller J (2013) RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts. Nat Rev Mol Cell Biol 14:699–712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goenka A, Sengupta S, Pandey R, Parihar R, Mohanta GC, Mukerji M, Ganesh S (2016) Human satellite-III non-coding RNAs modulate heat-shock-induced transcriptional repression. J Cell Sci 129:3541–3552

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guarnerio J, Bezzi M, Jeong JC, Paffenholz SV, Berry K, Naldini MM, Lo-Coco F, Tay Y, Beck AH, Pandolfi PP (2016) Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations. Cell 165:289–302

    Article  CAS  PubMed  Google Scholar 

  • Guttman M, Rinn JL (2012) Modular regulatory principles of large non-coding RNAs. Nature 482:339–346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hall LL, Byron M, Carone DM, Whitfield TW, Pouliot GP, Fischer A, Jones P, Lawrence JB (2017) Demethylated HSATII DNA and HSATII RNA foci sequester PRC1 and MeCP2 into cancer-specific nuclear bodies. Cell Rep 18:2943–2956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Hennig S, Kong G, Mannen T, Sadowska A, Kobelke S, Blythe A, Knott GJ, Iyer KS, Ho D, Newcombe EA, Hosoki K, Goshima N, Kawaguchi T, Hatters D, Trinkle-Mulcahy L, Hirose T, Bond CS, Fox AH (2015) Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles. J Cell Biol 210:529–539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirose T, Mishima Y, Tomari Y (2014a) Elements and machinery of non-coding RNAs: toward their taxonomy. EMBO Rep 15:489–507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirose T, Virnicchi G, Tanigawa A, Naganuma T, Li R, Kimura H, Yokoi T, Nakagawa S, Bénard M, Fox AH, Pierron G (2014b) NEAT1 long noncoding RNA regulates transcription via protein sequestration within subnuclear bodies. Mol Biol Cell 25:169–183

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ideue T, Hino K, Kitao S, Yokoi T, Hirose T (2009) Efficient oligonucleotide-mediated degradation of nuclear noncoding RNAs in mammalian cultured cells. RNA 15:1578–1587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Imamura K, Imamachi N, Akizuki G, Kumakura M, Kawaguchi A, Nagata K, Kato A, Kawaguchi Y, Sato H, Yoneda M, Kai C, Yada T, Suzuki Y, Yamada T, Ozawa T, Kaneki K, Inoue T, Kobayashi M, Kodama T, Wada Y, Sekimizu K, Akimitsu N (2014) Long noncoding RNA NEAT1-dependent SFPQ relocation from promoter region to paraspeckle mediates IL8 expression upon immune stimuli. Mol Cell 53:393–406

    Article  CAS  PubMed  Google Scholar 

  • Indrieri A, Grimaldi C, Zucchelli S, Tammaro R, Gustincich S, Franco B (2016) Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo. Sci Rep 6:27315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacob MD, Audas TE, Mullineux ST, Lee S (2012) Where no RNA polymerase has gone before: novel functional transcripts derived from the ribosomal intergenic spacer. Nucleus 3:315–319

    Article  PubMed  Google Scholar 

  • Jacob MD, Audas TE, Uniacke J, Trinkle-Mulcahy L, Lee S (2013) Environmental cues induce a long noncoding RNA-dependent remodeling of the nucleolus. Mol Biol Cell 24:2943–2953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jolly C, Lakhotia SC (2006) Human sat III and Drosophila hsr omega transcripts: a common paradigm for regulation of nuclear RNA processing in stressed cells. Nucleic Acids Res 34:5508–5514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaikkonen MU, Spann NJ, Heinz S, Romanoski CE, Allison KA, Stender JD, Chun HB, Tough DF, Prinjha RK, Benner C, Glass CK (2013) Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription. Mol Cell 51:310–325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanadia RN, Johnstone KA, Mankodi A, Lungu C, Thornton CA, Esson D, Timmers AM, Hauswirth WW, Swanson MS (2003) A muscleblind knockout model for myotonic dystrophy. Science 302:1978–1980

    Article  CAS  PubMed  Google Scholar 

  • Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermüller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316:1484–1488

    Article  CAS  PubMed  Google Scholar 

  • Kashi K, Henderson L, Bonetti A, Carninci P (2016) Discovery and functional analysis of lncRNAs: methodologies to investigate an uncharacterized transcriptome. Biochim Biophys Acta 1859:3–15

    Article  CAS  PubMed  Google Scholar 

  • Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, Nishida H, Yap CC, Suzuki M, Kawai J, Suzuki H, Carninci P, Hayashizaki Y, Wells C, Frith M, Ravasi T, Pang KC, Hallinan J, Mattick J, Hume DA, Lipovich L, Batalov S, Engström PG, Mizuno Y, Faghihi MA, Sandelin A, Chalk AM, Mottagui-Tabar S, Liang Z, Lenhard B, Wahlestedt C, RIKEN Genome Exploration Research Group, Genome Science Group (Genome Network Project Core Group), FANTOM Consortium (2005) Antisense transcription in the mammalian transcriptome. Science 309:1564–1566

    Article  PubMed  Google Scholar 

  • Kawaguchi T, Hirose T (2015) Chromatin remodeling complexes in the assembly of long noncoding RNA-dependent nuclear bodies. Nucleus 6:462–467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawaguchi T, Tanigawa A, Naganuma T, Ohkawa Y, Souquere S, Pierron G, Hirose T (2015) SWI/SNF chromatin-remodeling complexes function in noncoding RNA-dependent assembly of nuclear bodies. Proc Natl Acad Sci U S A 112:4304–4309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kishikawa T, Otsuka M, Yoshikawa T, Ohno M, Yamamoto K, Yamamoto N, Kotani A, Koike K (2016) Quantitation of circulating satellite RNAs in pancreatic cancer patients. JCI Insight 1:e86646

    Article  PubMed  PubMed Central  Google Scholar 

  • Kretz M, Siprashvili Z, Chu C, Webster DE, Zehnder A, Qu K, Lee CS, Flockhart RJ, Groff AF, Chow J, Johnston D, Kim GE, Spitale RC, Flynn RA, Zheng GX, Aiyer S, Raj A, Rinn JL, Chang HY, Khavari PA (2013) Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature 493:231–235

    Article  CAS  PubMed  Google Scholar 

  • Lee M, Sadowska A, Bekere I, Ho D, Gully BS, Lu Y, Iyer KS, Trewhella J, Fox AH, Bond CS (2015) The structure of human SFPQ reveals a coiled-coil mediated polymer essential for functional aggregation in gene regulation. Nucleic Acids Res 43:3826–3840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee S, Kopp F, Chang TC, Sataluri A, Chen B, Sivakumar S, Yu H, Xie Y, Mendell JT (2016) Noncoding RNA NORAD regulates genomic stability by sequestering PUMILIO proteins. Cell 164:69–80

    Article  CAS  PubMed  Google Scholar 

  • Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O, Fatica A, Santini T, Andronache A, Wade M, Laneve P, Rajewsky N, Bozzoni I (2017) Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis. Mol Cell 66:22–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li R, Harvey AR, Hodgetts SI, Fox AH (2017) Functional dissection of NEAT1 using genome editing reveals substantial localization of the NEAT1_1 isoform outside paraspeckles. RNA 23:872–881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang D, Wilusz JE (2014) Short intronic repeat sequences facilitate circular RNA production. Genes Dev 28:2233–2247

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu SJ, Horlbeck MA, Cho SW, Birk HS, Malatesta M, He D, Attenello FJ, Villalta JE, Cho MY, Chen Y, Mandegar MA, Olvera MP, Gilbert LA, Conklin BR, Chang HY, Weissman JS, Lim DA (2017) CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells. Science 355:aah7111

    Article  PubMed  CAS  Google Scholar 

  • Lu Z, Chang HY (2016) Decoding the RNA structurome. Curr Opin Struct Biol 36:142–148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma H, Han P, Ye W, Chen H, Zheng X, Cheng L, Zhang L, Yu L, Wu X, Xu Z, Lei Y, Zhang F (2017) The long noncoding RNA NEAT1 exerts antihantaviral effects by acting as positive feedback for RIG-I signaling. J Virol 91:e02250–e02216

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mannen T, Yamashita S, Tomita K, Goshima N, Hirose T (2016) The Sam68 nuclear body is composed of two RNase-sensitive substructures joined by the adaptor HNRNPL. J Cell Biol 214:45–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto A, Pasut A, Matsumoto M, Yamashita R, Fung J, Monteleone E, Saghatelian A, Nakayama KI, Clohessy JG, Pandolfi PP (2017) mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide. Nature 541:228–232

    Article  CAS  PubMed  Google Scholar 

  • McHugh CA, Chen CK, Chow A, Surka CF, Tran C, McDonel P, Pandya-Jones A, Blanco M, Burghard C, Moradian A, Sweredoski MJ, Shishkin AA, Su J, Lander ES, Hess S, Plath K, Guttman M (2015) The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. Nature 521:232–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, Loewer A, Ziebold U, Landthaler M, Kocks C, le Noble F, Rajewsky N (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495:333–338

    Article  CAS  PubMed  Google Scholar 

  • Mohan A, Goodwin M, Swanson MS (2014) RNA-protein interactions in unstable microsatellite diseases. Brain Res 1584:3–14

    Article  CAS  PubMed  Google Scholar 

  • Naganuma T, Nakagawa S, Tanigawa A, Sasaki YF, Goshima N, Hirose T (2012) Alternative 3′-end processing of long noncoding RNA initiates construction of nuclear paraspeckles. EMBO J 31:4020–4034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakagawa S, Shimada M, Yanaka K, Mito M, Arai T, Takahashi E, Fujita Y, Fujimori T, Standaert L, Marine JC, Hirose T (2014) The lncRNA Neat1 is required for corpus luteum formation and the establishment of pregnancy in a subpopulation of mice. Development 141:4618–4627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson DL, Orr HT, Warren ST (2013) The unstable repeats--three evolving faces of neurological disease. Neuron 77:825–843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson BR, Makarewich CA, Anderson DM, Winders BR, Troupes CD, Wu F, Reese AL, McAnally JR, Chen X, Kavalali ET, Cannon SC, Houser SR, Bassel-Duby R, Olson EN (2016) A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. Science 351:271–275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishimoto Y, Nakagawa S, Hirose T, Okano HJ, Takao M, Shibata S, Suyama S, Kuwako K, Imai T, Murayama S, Suzuki N, Okano H (2013) The long non-coding RNA nuclear-enriched abundant transcript 1_2 induces paraspeckle formation in the motor neuron during the early phase of amyotrophic lateral sclerosis. Mol Brain 6:31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paralkar VR, Taborda CC, Huang P, Yao Y, Kossenkov AV, Prasad R, Luan J, Davies JO, Hughes JR, Hardison RC, Blobel GA, Weiss MJ (2016) Unlinking an lncRNA from its associated cis element. Mol Cell 62:104–110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Passon DM, Lee M, Rackham O, Stanley WA, Sadowska A, Filipovska A, Fox AH, Bond CS (2012) Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation. Proc Natl Acad Sci U S A 109:4846–4850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641

    Article  CAS  PubMed  Google Scholar 

  • Prasanth KV, Prasanth SG, Xuan Z, Hearn S, Freier SM, Bennett CF, Zhang MQ, Spector DL (2005) Regulating gene expression through RNA nuclear retention. Cell 123:249–263

    Article  CAS  PubMed  Google Scholar 

  • Quinn JJ, Chang HY (2016) Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet 17:47–62

    Article  CAS  PubMed  Google Scholar 

  • Ramaswami M, Taylor JP, Parker R (2013) Altered ribostasis: RNA-protein granules in degenerative disorders. Cell 154:727–736

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Saha S, Sugumar P, Bhandari P, Rangarajan PN (2006) Identification of Japanese encephalitis virus-inducible genes in mouse brain and characterization of GARG39/IFIT2 as a microtubule-associated protein. J Gen Virol 87:3285–3289

    Article  CAS  PubMed  Google Scholar 

  • Salzman J (2016) Circular RNA expression: its potential regulation and function. Trends Genet 32:309–316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarma K, Levasseur P, Aristarkhov A, Lee JT (2010) Locked nucleic acids (LNAs) reveal sequence requirements and kinetics of Xist RNA localization to the X chromosome. Proc Natl Acad Sci U S A 107:22196–22201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasaki YT, Ideue T, Sano M, Mituyama T, Hirose T (2009) MENepsilon/beta noncoding RNAs are essential for structural integrity of nuclear paraspeckles. Proc Natl Acad Sci U S A 106:2525–2530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmitt AM, Chang HY (2016) Long noncoding RNAs in cancer pathways. Cancer Cell 29:452–463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen W, Liang XH, Crooke ST (2014) Phosphorothioate oligonucleotides can displace NEAT1 RNA and form nuclear paraspeckle-like structures. Nucleic Acids Res 42:8648–8662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shevtsov SP, Dundr M (2011) Nucleation of nuclear bodies by RNA. Nat Cell Biol 13:167–173

    Article  CAS  PubMed  Google Scholar 

  • Souquere S, Beauclair G, Harper F, Fox A, Pierron G (2010) Highly ordered spatial organization of the structural long noncoding NEAT1 RNAs within paraspeckle nuclear bodies. Mol Biol Cell 21:4020–4027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Standaert L, Adriaens C, Radaelli E, Van Keymeulen A, Blanpain C, Hirose T, Nakagawa S, Marine JC (2014) The long noncoding RNA Neat1 is required for mammary gland development and lactation. RNA 20:1844–1849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steitz J (2015) RNA-RNA base-pairing: theme and variations. RNA 21:476–477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sunwoo H, Dinger ME, Wilusz JE, Amaral PP, Mattick JS, Spector DL (2009) MEN epsilon/beta nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles. Genome Res 19:347–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sunwoo JS, Lee ST, Im W, Lee M, Byun JI, Jung KH, Park KI, Jung KY, Lee SK, Chu K, Kim M (2017) Altered expression of the long noncoding RNA NEAT1 in Huntington’s disease. Mol Neurobiol 54:1577–1586

    Article  CAS  PubMed  Google Scholar 

  • Takahashi H, Carninci P (2014) Widespread genome transcription: new possibilities for RNA therapies. Biochem Biophys Res Commun 452:294–301

    Article  CAS  PubMed  Google Scholar 

  • Taniue K, Kurimoto A, Sugimasa H, Nasu E, Takeda Y, Iwasaki K, Nagashima T, Okada-Hatakeyama M, Oyama M, Kozuka-Hata H, Hiyoshi M, Kitayama J, Negishi L, Kawasaki Y, Akiyama T (2016) Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1. Proc Natl Acad Sci U S A 113:1273–1278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taylor JP, Brown RH Jr, Cleveland DW (2016) Decoding ALS: from genes to mechanism. Nature 539:197–206

    Article  PubMed  PubMed Central  Google Scholar 

  • Ting DT, Lipson D, Paul S, Brannigan BW, Akhavanfard S, Coffman EJ, Contino G, Deshpande V, Iafrate AJ, Letovsky S, Rivera MN, Bardeesy N, Maheswaran S, Haber DA (2011) Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers. Science 331:593–596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, König J, Hortobágyi T, Nishimura AL, Zupunski V, Patani R, Chandran S, Rot G, Zupan B, Shaw CE, Ule J (2011) Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci 14:452–458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsuiji H, Iguchi Y, Furuya A, Kataoka A, Hatsuta H, Atsuta N, Tanaka F, Hashizume Y, Akatsu H, Murayama S, Sobue G, Yamanaka K (2013) Spliceosome integrity is defective in the motor neuron diseases ALS and SMA. EMBO Mol Med 5:221–234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tycowski KT, Shu MD, Borah S, Shi M, Steitz JA (2012) Conservation of a triple-helix-forming RNA stability element in noncoding and genomic RNAs of diverse viruses. Cell Rep 2:26–32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tycowski KT, Shu MD, Steitz JA (2016) Myriad triple-helix-forming structures in the transposable element RNAs of plants and fungi. Cell Rep 15:1266–1276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ulitsky I, Bartel DP (2013) lincRNAs: genomics, evolution, and mechanisms. Cell 154:26–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uversky VN (2016) Intrinsically disordered proteins in overcrowded milieu: membrane-less organelles, phase separation, and intrinsic disorder. Curr Opin Struct Biol 44:18–30

    Article  PubMed  CAS  Google Scholar 

  • Valgardsdottir R, Chiodi I, Giordano M, Rossi A, Bazzini S, Ghigna C, Riva S, Biamonti G (2008) Transcription of Satellite III non-coding RNAs is a general stress response in human cells. Nucleic Acids Res 36:423–434

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • West JA, Davis CP, Sunwoo H, Simon MD, Sadreyev RI, Wang PI, Tolstorukov MY, Kingston RE (2014) The long noncoding RNAs NEAT1 and MALAT1 bind active chromatin sites. Mol Cell 55:791–802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • West JA, Mito M, Kurosaka S, Takumi T, Tanegashima C, Chujo T, Yanaka K, Kingston RE, Hirose T, Bond C, Fox A, Nakagawa S (2016) Structural, super-resolution microscopy analysis of paraspeckle nuclear body organization. J Cell Biol 214:817–830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilusz JE, Freier SM, Spector D (2008) 3′ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell 135:919–932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wojciechowska M, Krzyzosiak WJ (2011) Cellular toxicity of expanded RNA repeats: focus on RNA foci. Hum Mol Genet 20:3811–3821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu H (2013) Higher-order assemblies in a new paradigm of signal transduction. Cell 153:287–292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamazaki T, Hirose T (2015) The building process of the functional paraspeckle with long non-coding RNAs. Front Biosci (Elite Ed) 7:1–41

    Article  Google Scholar 

  • Yoon JH, Abdelmohsen K, Kim J, Yang X, Martindale JL, Tominaga-Yamanaka K, White EJ, Orjalo AV, Rinn JL, Kreft SG, Wilson GM, Gorospe M (2013) Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination. Nat Commun 4:2939

    Article  PubMed  CAS  Google Scholar 

  • Zhang Q, Chen CY, Yedavalli VS, Jeang KT (2013) NEAT1 long noncoding RNA and paraspeckle bodies modulate HIV-1 posttranscriptional expression. MBio 4:e00596–e00512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zucchelli S, Cotella D, Takahashi H, Carrieri C, Cimatti L, Fasolo F, Jones MH, Sblattero D, Sanges R, Santoro C, Persichetti F, Carninci P, Gustincich S (2015a) SINEUPs: a new class of natural and synthetic antisense long non-coding RNAs that activate translation. RNA Biol 12:771–779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zucchelli S, Fasolo F, Russo R, Cimatti L, Patrucco L, Takahashi H, Jones MH, Santoro C, Sblattero D, Cotella D, Persichetti F, Carninci P, Gustincich S (2015b) SINEUPs are modular antisense long non-coding RNAs that increase synthesis of target proteins in cells. Front Cell Neurosci 9:174

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zucchelli S, Patrucco L, Persichetti F, Gustincich S, Cotella D (2016) Engineering translation in mammalian cell factories to increase protein yield: the unexpected use of long non-coding SINEUP RNAs. Comput Struct Biotechnol J 14:404–410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Yamazaki, T. (2018). Long Noncoding RNAs and Their Applications: Focus on Architectural RNA (arcRNA), a Class of lncRNA. In: Masuda, S., Izawa, S. (eds) Applied RNA Bioscience. Springer, Singapore. https://doi.org/10.1007/978-981-10-8372-3_11

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