title: LncRNA OIP5-AS1/cyrano sponges RNA-binding protein HuR.
abstract: The function of the vast majority of mammalian long noncoding (lnc) RNAs remains unknown. Here, analysis of a highly abundant mammalian lncRNA, OIP5-AS1, known as cyrano in zebrafish, revealed that OIP5-AS1 reduces cell proliferation. In human cervical carcinoma HeLa cells, the RNA-binding protein HuR, which enhances cell proliferation, associated with OIP5-AS1 and stabilized it. Tagging OIP5-AS1 with MS2 hairpins to identify associated microRNAs revealed that miR-424 interacted with OIP5-AS1 and competed with HuR for binding to OIP5-AS1. We further identified a 'sponge' function for OIP5-AS1, as high levels of OIP5-AS1 increased HuR-OIP5-AS1 complexes and prevented HuR interaction with target mRNAs, including those that encoded proliferative proteins, while conversely, lowering OIP5-AS1 increased the abundance of HuR complexes with target mRNAs. We propose that OIP5-AS1 serves as a sponge or a competing endogenous (ce)RNA for HuR, restricting its availability to HuR target mRNAs and thereby repressing HuR-elicited proliferative phenotypes.
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA.
authors.forename: Kotb
authors.initials: K
authors.lastname: Abdelmohsen
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA.
authors.forename: Supriyo
authors.initials: S
authors.lastname: De
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Grammatikakis
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA.
authors.forename: Ji Heon
authors.initials: JH
authors.lastname: Noh
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA gorospem@grc.nia.nih.gov.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D049109:Cell Proliferation / Q000235:genetics; D000067780:ELAV-Like Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C554214:MIRN424 microrna, human; D008565:Membrane Proteins; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D051722:ADAM Proteins; C068490:ADAM8 protein, human
references.citation: EMBO J. 2009 May 6;28(9):1271-82
references.pmid: 19322201
references.citation: Genes Dev. 2009 Aug 1;23(15):1743-8
references.pmid: 19574298
references.citation: J Biol Chem. 2010 Feb 12;285(7):4432-40
references.pmid: 20018854
references.citation: Annu Rev Biochem. 2010;79:351-79
references.pmid: 20533884
references.citation: Brain Res. 2010 Jun 18;1338:20-35
references.pmid: 20380817
references.citation: Nature. 2010 Jun 24;465(7301):1033-8
references.pmid: 20577206
references.citation: PLoS One. 2010;5(10):e13599
references.pmid: 21049042
references.citation: EMBO J. 2011 Mar 16;30(6):1040-53
references.pmid: 21317874
references.citation: Nucleic Acids Res. 2011 Apr;39(8):3026-41
references.pmid: 21149267
references.citation: Nat Methods. 2007 Sep;4(9):721-6
references.pmid: 17694064
references.citation: J Cell Biol. 2008 Jan 14;180(1):113-27
references.pmid: 18180367
references.citation: Nat Methods. 2011 Jul;8(7):559-64
references.pmid: 21572407
references.citation: Cell. 2011 Aug 5;146(3):353-8
references.pmid: 21802130
references.citation: Mol Cell. 2011 Aug 5;43(3):327-39
references.pmid: 21723170
references.citation: Mol Cell. 2011 Aug 5;43(3):340-52
references.pmid: 21723171
references.citation: Mol Cell Biol. 2011 Sep;31(18):3790-801
references.pmid: 21768308
references.citation: Semin Cell Dev Biol. 2011 Jun;22(4):366-76
references.pmid: 21256239
references.citation: Cancer Res. 2001 Mar 1;61(5):2154-61
references.pmid: 11280780
references.citation: J Clin Invest. 2001 Dec;108(11):1657-65
references.pmid: 11733561
references.citation: Mol Cell Biol. 2002 May;22(10):3425-36
references.pmid: 11971974
references.citation: J Biol Chem. 2002 Nov 22;277(47):44623-30
references.pmid: 12237300
references.citation: Mol Cell Biol. 1982 Jun;2(6):701-7
references.pmid: 14582165
references.citation: J Mol Biol. 1968 Dec;38(3):289-304
references.pmid: 5718554
references.citation: Mol Cell Biochem. 1975 Oct 31;9(1):9-16
references.pmid: 1186664
references.citation: Science. 2005 Sep 2;309(5740):1514-8
references.pmid: 16141059
references.citation: Cell. 2006 Jun 16;125(6):1111-24
references.pmid: 16777601
references.citation: Mol Cell. 2007 Feb 23;25(4):543-57
references.pmid: 17317627
references.citation: Mol Biol Cell. 2007 Jun;18(6):2137-48
references.pmid: 17392515
references.citation: Cell. 2011 Oct 14;147(2):358-69
references.pmid: 22000014
references.citation: Nat Rev Genet. 2011 Dec;12(12):861-74
references.pmid: 22094949
references.citation: Cell. 2011 Dec 23;147(7):1537-50
references.pmid: 22196729
references.citation: Front Biosci (Landmark Ed). 2012;17:189-205
references.pmid: 22201738
references.citation: Annu Rev Biochem. 2012;81:145-66
references.pmid: 22663078
references.citation: Cell. 2012 Jun 8;149(6):1393-406
references.pmid: 22658674
references.citation: Wiley Interdiscip Rev RNA. 2010 Sep-Oct;1(2):214-29
references.pmid: 21935886
references.citation: Curr Protein Pept Sci. 2012 Jun;13(4):380-90
references.pmid: 22708484
references.citation: Histol Histopathol. 2010 Oct;25(10):1331-40
references.pmid: 20712017
references.citation: Nucleic Acids Res. 2010 Sep;38(16):5366-83
references.pmid: 20423907
references.citation: Wiley Interdiscip Rev Syst Biol Med. 2010 Mar-Apr;2(2):162-80
references.pmid: 20836020
references.citation: Curr Protein Pept Sci. 2012 Jun;13(4):372-9
references.pmid: 22708488
references.citation: Mol Cell. 2012 Aug 24;47(4):648-55
references.pmid: 22841487
references.citation: Genome Res. 2012 Sep;22(9):1775-89
references.pmid: 22955988
references.citation: RNA Biol. 2012 Jun;9(6):703-19
references.pmid: 22664915
references.citation: Oncogene. 2013 Feb 21;32(8):976-87
references.pmid: 22469983
references.citation: Cell. 2013 Jul 3;154(1):26-46
references.pmid: 23827673
references.citation: J Mol Biol. 2013 Oct 9;425(19):3723-30
references.pmid: 23178169
references.citation: Aging Cell. 2013 Oct;12(5):890-900
references.pmid: 23758631
references.citation: Pathol Oncol Res. 2013 Oct;19(4):739-48
references.pmid: 23653113
references.citation: Cell Rep. 2013 Nov 27;5(4):909-17
references.pmid: 24210824
references.citation: Nature. 2014 Jan 16;505(7483):344-52
references.pmid: 24429633
references.citation: Crit Rev Biochem Mol Biol. 2014 Jan-Feb;49(1):16-32
references.pmid: 24164576
references.citation: ScientificWorldJournal. 2014;2014:178075
references.pmid: 24516357
references.citation: PLoS One. 2014;9(3):e91661
references.pmid: 24675898
references.citation: Mol Cancer. 2014;13:92
references.pmid: 24775712
references.citation: Nat Rev Mol Cell Biol. 2014 Aug;15(8):509-24
references.pmid: 25027649
references.citation: Genome Biol. 2014;15(1):R6
references.pmid: 24393600
references.citation: Nucleic Acids Res. 2014 Sep;42(15):10099-111
references.pmid: 25123665
references.citation: Annu Rev Genet. 2014;48:433-55
references.pmid: 25251851
references.citation: Mutat Res Rev Mutat Res. 2014 Oct-Dec;762:1-21
references.pmid: 25485593
references.citation: Aging (Albany NY). 2014 Dec;6(12):992-1009
references.pmid: 25543668
references.citation: RNA Biol. 2014;11(10):1250-61
references.pmid: 25584704
references.citation: Oncol Rep. 2015 May;33(5):2354-60
references.pmid: 25708247
references.citation: Genome Biol. 2015;16:20
references.pmid: 25630241
references.citation: Nucleic Acids Res. 2015 Apr 20;43(7):3478-89
references.pmid: 25800746
references.citation: J Mol Cell Cardiol. 2015 Jun;83:142-55
references.pmid: 25640162
references.citation: Oncotarget. 2015 Sep 8;6(26):22513-25
references.pmid: 26068968
references.citation: Nucleic Acids Res. 2016 Jan 29;44(2):863-77
references.pmid: 26578588
references.citation: Nucleic Acids Res. 2008 Mar;36(4):1390-9
references.pmid: 18203745
references.citation: Mol Cell Biol. 2008 Apr;28(8):2608-25
references.pmid: 18285462
references.citation: Cell Mol Life Sci. 2008 Oct;65(20):3168-81
references.pmid: 18581050
references.citation: Cell Cycle. 2008 Oct;7(20):3124-6
references.pmid: 18927508
references.citation: Gastroenterology. 2008 Dec;135(6):2030-42, 2042.e1-3
references.pmid: 18824170
references.citation: Cell Cycle. 2008 Nov 1;7(21):3371-7
references.pmid: 18948743