title: Non-coding RNA: a new frontier in regulatory biology.
abstract: A striking finding in the past decade is the production of numerous non-coding RNAs (ncRNAs) from mammalian genomes. While it is entirely possible that many of those ncRNAs are transcription noises or by-products of RNA processing, increasing evidence suggests that a large fraction of them are functional and provide various regulatory activities in the cell. Thus, functional genomics and proteomics are incomplete without understanding functional ribonomics. As has been long suggested by the 'RNA world' hypothesis, many ncRNAs have the capacity to act like proteins in diverse biochemical processes. The enormous amount of information residing in the primary sequences and secondary structures of ncRNAs makes them particularly suited to function as scaffolds for molecular interactions. In addition, their functions appear to be stringently controlled by default via abundant nucleases when not engaged in specific interactions. This review focuses on the functional properties of regulatory ncRNAs in comparison with proteins and emphasizes both the opportunities and challenges in future ncRNA research.
authors.affiliation: Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Fu
keywords: biological functions; experimental approaches; functional genomics; non-coding RNA; regulatory mechanisms; the RNA world
references.citation: Cell. 2013 Jul 3;154(1):26-46
references.pmid: 23827673
references.citation: Cell. 2013 Mar 14;152(6):1308-23
references.pmid: 23498939
references.citation: Cell. 2014 Feb 27;156(5):907-19
references.pmid: 24581492
references.citation: Nat Cell Biol. 2011 Apr;13(4):423-33
references.pmid: 21423178
references.citation: Nature. 2014 Jan 30;505(7485):706-9
references.pmid: 24476892
references.citation: Cell. 2013 Apr 25;153(3):654-65
references.pmid: 23622248
references.citation: Nature. 2012 Sep 6;489(7414):91-100
references.pmid: 22955619
references.citation: Science. 2008 Mar 28;319(5871):1791-2
references.pmid: 18369138
references.citation: Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19202-7
references.pmid: 23129630
references.citation: Nat Struct Mol Biol. 2013 Nov;20(11):1258-64
references.pmid: 24141703
references.citation: Mol Cell. 2010 Jul 9;39(1):133-44
references.pmid: 20603081
references.citation: Mol Cell. 2013 Sep 26;51(6):792-806
references.pmid: 24035497
references.citation: Cell. 2013 Dec 19;155(7):1479-91
references.pmid: 24360272
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D290-301
references.pmid: 22127870
references.citation: Nucleic Acids Res. 2014 Jan;42(Database issue):D92-7
references.pmid: 24297251
references.citation: Nat Med. 2008 Jul;14(7):723-30
references.pmid: 18587408
references.citation: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Oct 1;66(Pt 10):1148-52
references.pmid: 20944204
references.citation: Nature. 2014 Jan 30;505(7485):701-5
references.pmid: 24336214
references.citation: Cell Res. 2012 Jan;22(1):107-26
references.pmid: 21931358
references.citation: Dev Cell. 2013 Jan 28;24(2):206-14
references.pmid: 23369715
references.citation: Science. 1997 Apr 25;276(5312):614-7
references.pmid: 9110984
references.citation: Cell. 2013 Mar 14;152(6):1298-307
references.pmid: 23498938
references.citation: Nature. 2011 Apr 7;472(7341):120-4
references.pmid: 21423168
references.citation: Nature. 2013 Jun 27;498(7455):511-5
references.pmid: 23728303
references.citation: Cell. 2012 Jun 8;149(6):1393-406
references.pmid: 22658674
references.citation: Nature. 2013 Jul 18;499(7458):360-3
references.pmid: 23792564
references.citation: Genes Dev. 2010 Oct 15;24(20):2264-9
references.pmid: 20952535
references.citation: Genes Dev. 2012 Nov 15;26(22):2550-9
references.pmid: 23154985
references.citation: Genome Res. 2012 Sep;22(9):1775-89
references.pmid: 22955988
references.citation: Cell. 2013 Jul 3;154(1):240-51
references.pmid: 23810193
references.citation: Nat Neurosci. 2012 Jun;15(6):827-35
references.pmid: 22610069
references.citation: Genes Dev. 2013 Jun 1;27(11):1260-71
references.pmid: 23723417
references.citation: Sci Signal. 2010 Feb 02;3(107):ra8
references.pmid: 20124551
references.citation: Mol Cell. 2009 Mar 27;33(6):717-26
references.pmid: 19217333
references.citation: Cold Spring Harb Perspect Biol. 2010 Dec;2(12):a000711
references.pmid: 21068152
references.citation: Nature. 2006 Sep 21;443(7109):302-7
references.pmid: 16943774
references.citation: Nature. 1989 Mar 16;338(6212):217-24
references.pmid: 2466202
references.citation: Mol Cell. 2012 Mar 9;45(5):656-68
references.pmid: 22325991
references.citation: Nat Methods. 2008 Jul;5(7):621-8
references.pmid: 18516045
references.citation: Science. 2008 Dec 19;322(5909):1845-8
references.pmid: 19056941
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19199-204
references.pmid: 19052240
references.citation: Curr Opin Genet Dev. 2009 Oct;19(5):424-36
references.pmid: 19846290
references.citation: Nature. 2009 Mar 12;458(7235):223-7
references.pmid: 19182780
references.citation: Genome Res. 2012 Sep;22(9):1646-57
references.pmid: 22955977
references.citation: Science. 2010 Aug 6;329(5992):689-93
references.pmid: 20616235
references.citation: Nat Struct Mol Biol. 2013 Nov;20(11):1250-7
references.pmid: 24077223
references.citation: Mol Cell. 2008 Feb 29;29(4):499-509
references.pmid: 18313387
references.citation: Nature. 2013 Mar 21;495(7441):333-8
references.pmid: 23446348
references.citation: Nature. 2011 Feb 10;470(7333):284-8
references.pmid: 21307942
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D348-52
references.pmid: 23197659
references.citation: Annu Rev Cell Dev Biol. 2009;25:355-76
references.pmid: 19575643
references.citation: Nature. 2002 Jul 11;418(6894):222-8
references.pmid: 12110898
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):E2110-6
references.pmid: 22753494
references.citation: Nat Rev Genet. 2012 Mar 13;13(4):271-82
references.pmid: 22411466
references.citation: Methods Mol Biol. 2014;1125:169-78
references.pmid: 24590789
references.citation: Mol Cell. 2014 Feb 20;53(4):549-61
references.pmid: 24508389
references.citation: Cell Rep. 2012 Jul 26;2(1):111-23
references.pmid: 22840402
references.citation: Science. 2008 Dec 19;322(5909):1849-51
references.pmid: 19056940
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 24;109 (30):11944-8
references.pmid: 22786931
references.citation: Mol Cells. 2014 Jan;37(1):1-8
references.pmid: 24552703
references.citation: Mol Cell Biol. 2006 Jan;26(2):630-42
references.pmid: 16382153
references.citation: Nature. 2007 Feb 8;445(7128):666-70
references.pmid: 17237763
references.citation: Genes Dev. 2012 Nov 1;26(21):2392-407
references.pmid: 23073843
references.citation: Science. 2013 Aug 16;341(6147):1237973
references.pmid: 23828888
references.citation: Cell. 1999 Apr 2;97(1):17-27
references.pmid: 10199399
references.citation: Nat Genet. 2010 Dec;42(12):1113-7
references.pmid: 21057500
references.citation: Nature. 2011 Aug 28;477(7364):295-300
references.pmid: 21874018
references.citation: Nat Cell Biol. 2011 Jan;13(1):95-101
references.pmid: 21170033
references.citation: Development. 2013 Jul;140(13):2828-34
references.pmid: 23698349
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D226-32
references.pmid: 23125362
references.citation: Cell Rep. 2012 May 31;1(5):570-81
references.pmid: 22708079
references.citation: J Genet Genomics. 2013 Jun 20;40(6):281-9
references.pmid: 23790627
references.citation: Cell. 2013 Jan 31;152(3):570-83
references.pmid: 23352431
references.citation: Nature. 2012 Sep 6;489(7414):57-74
references.pmid: 22955616
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11667-72
references.pmid: 19571010
references.citation: Nature. 2013 Jan 31;493(7434):638-43
references.pmid: 23354046
references.citation: Annu Rev Genet. 2013;47:139-65
references.pmid: 24274751
references.citation: Annu Rev Biochem. 2010;79:351-79
references.pmid: 20533884
references.citation: Biochem Soc Symp. 1982;47:183-91
references.pmid: 6100822
references.citation: Nat Rev Genet. 2011 Nov 18;12(12):861-74
references.pmid: 22094949
references.citation: Nature. 2013 Jun 27;498(7455):516-20
references.pmid: 23728302
references.citation: Nature. 2011 Dec 14;481(7380):190-4
references.pmid: 22170610
references.citation: Nat Rev Genet. 2011 Jan;12(1):19-31
references.pmid: 21116305
references.citation: Science. 2006 Feb 24;311(5764):1118-23
references.pmid: 16497925
references.citation: Cell. 2013 Dec 19;155(7):1581-95
references.pmid: 24360279
references.citation: Nature. 1990 Feb 1;343(6257):437-41
references.pmid: 2137203
references.citation: Nat Rev Genet. 2012 Jan 18;13(2):77-83
references.pmid: 22251872
references.citation: Nature. 1991 Jan 3;349(6304):38-44
references.pmid: 1985261
references.citation: Trends Biochem Sci. 2006 Jun;31(6):333-41
references.pmid: 16679018
references.citation: Ann Neurol. 2013 Jun;73(6):729-40
references.pmid: 23494648
references.citation: Nature. 2009 Oct 8;461(7265):754-61
references.pmid: 19812667
references.citation: Nature. 2008 Nov 13;456(7219):209-13
references.pmid: 18754009
references.citation: EMBO J. 2012 Oct 17;31(20):4020-34
references.pmid: 22960638
references.citation: Nature. 2010 May 13;465(7295):182-7
references.pmid: 20393465
references.citation: Cell. 2009 Feb 20;136(4):656-68
references.pmid: 19239887
references.citation: Cell. 2011 Aug 5;146(3):353-8
references.pmid: 21802130
references.citation: Nat Chem Biol. 2013 Jan;9(1):18-20
references.pmid: 23178934
references.citation: Mol Cell. 2013 Oct 10;52(1):101-12
references.pmid: 24055342
references.citation: Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20497-502
references.pmid: 22143764
references.citation: Mol Cell. 2014 Feb 6;53(3):393-406
references.pmid: 24507715
references.citation: Science. 2010 Nov 26;330(6008):1244-7
references.pmid: 21109672
references.citation: J Cell Biol. 2011 Apr 4;193(1):31-9
references.pmid: 21444682
references.citation: Nature. 2013 Feb 28;494(7438):497-501
references.pmid: 23417068
references.citation: RNA. 2007 Jun;13(6):868-80
references.pmid: 17456562
references.citation: Nat Biotechnol. 2013 Nov;31(11):965-7
references.pmid: 24213763
references.citation: Genome Res. 2008 Sep;18(9):1433-45
references.pmid: 18562676
references.citation: Mol Cell. 2013 Feb 7;49(3):524-35
references.pmid: 23273978
references.citation: Cell. 2013 Feb 14;152(4):727-42
references.pmid: 23415223
references.citation: Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5416-21
references.pmid: 23493562
references.citation: Cell Rep. 2014 Jan 16;6(1):222-30
references.pmid: 24388749
references.citation: Nat Rev Genet. 2014 Jan;15(1):7-21
references.pmid: 24296535
references.citation: Nature. 2013 Aug 29;500(7464):598-602
references.pmid: 23945587
references.citation: Nat Genet. 2011 Jun 05;43(7):621-9
references.pmid: 21642992
references.citation: Curr Opin Cell Biol. 2013 Apr;25(2):190-4
references.pmid: 23465540
references.citation: EMBO J. 2012 Mar 21;31(6):1579-90
references.pmid: 22314233
references.citation: RNA. 2010 Feb;16(2):324-37
references.pmid: 20026622
references.citation: Cell. 2013 May 9;153(4):855-68
references.pmid: 23663783
references.citation: Curr Biol. 2002 Jan 8;12(1):13-25
references.pmid: 11790299
references.citation: Nat Protoc. 2013 Nov;8(11):2180-96
references.pmid: 24136345
references.citation: Front Genet. 2013 Sep 05;4:173
references.pmid: 24046777
references.citation: Wiley Interdiscip Rev RNA. 2010 Jul-Aug;1(1):2-21
references.pmid: 21956903
references.citation: Mol Cell. 2009 Jul 10;35(1):1-10
references.pmid: 19595711
references.citation: Nature. 2013 Mar 21;495(7441):384-8
references.pmid: 23446346
references.citation: J Cell Biol. 2009 Sep 7;186(5):637-44
references.pmid: 19720872
references.citation: Cell. 2010 Oct 1;143(1):46-58
references.pmid: 20887892
references.citation: Mol Cell. 2010 Sep 24;39(6):925-38
references.pmid: 20797886
references.citation: Mol Cell. 2009 Aug 28;35(4):467-78
references.pmid: 19716791
references.citation: Annu Rev Biochem. 2012;81:145-66
references.pmid: 22663078
references.citation: Nat Methods. 2013 Oct;10(10):957-63
references.pmid: 24076990
references.citation: Nat Rev Mol Cell Biol. 2013 Feb;14(2):69-82
references.pmid: 23299958
references.citation: Nature. 2011 May 15;474(7351):390-4
references.pmid: 21572438
references.citation: Cell. 2006 Sep 22;126(6):1065-77
references.pmid: 16962654
references.citation: BMC Genomics. 2007 Feb 01;8:39
references.pmid: 17270048
references.citation: Cell. 2008 Nov 28;135(5):919-32
references.pmid: 19041754
references.citation: Dev Cell. 2013 Jan 14;24(1):13-25
references.pmid: 23328397
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D210-5
references.pmid: 22135294
references.citation: Nat Biotechnol. 2009 Jul;27(7):667-70
references.pmid: 19561594
references.citation: Science. 2006 Sep 29;313(5795):1935-42
references.pmid: 16959973
references.citation: Elife. 2013 Dec 31;2:e01749
references.pmid: 24381249
references.citation: Nature. 2002 Jul 11;418(6894):229-35
references.pmid: 12110899
references.citation: Mol Cell. 2011 Nov 18;44(4):667-78
references.pmid: 21963238
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2240-5
references.pmid: 23345452
references.citation: Trends Biochem Sci. 2014 Jan;39(1):35-43
references.pmid: 24290031
references.citation: Mol Cell. 2012 Oct 26;48(2):219-30
references.pmid: 22959273
references.citation: Cell. 2013 Jul 18;154(2):442-51
references.pmid: 23849981
references.citation: Cell. 2005 Oct 21;123(2):249-63
references.pmid: 16239143
references.citation: Nat Struct Mol Biol. 2013 Aug;20(8):936-43
references.pmid: 23832275
references.citation: Nat Rev Genet. 2001 Dec;2(12):919-29
references.pmid: 11733745
references.citation: Cell. 2006 Nov 17;127(4):735-45
references.pmid: 17110333
references.citation: Cancer Res. 2013 Feb 1;73(3):1180-9
references.pmid: 23243023
references.citation: Cold Spring Harb Perspect Biol. 2011 Feb 01;3(2):null
references.pmid: 20926517
references.citation: Genetics. 2007 Jun;176(2):1299-306
references.pmid: 17409075
references.citation: Science. 2001 May 18;292(5520):1319-25
references.pmid: 11358999
references.citation: Nature. 2008 Dec 18;456(7224):921-6
references.pmid: 19092929
references.citation: Nat Rev Genet. 2012 Oct;13(10):720-31
references.pmid: 22986266
references.citation: Nature. 2013 Jan 10;493(7431):231-5
references.pmid: 23201690
references.citation: Nature. 2013 Dec 19;504(7480):465-9
references.pmid: 24162848
references.citation: Cell. 2011 Nov 11;147(4):773-88
references.pmid: 22078878
references.citation: Nat Rev Mol Cell Biol. 2007 Jun;8(6):479-90
references.pmid: 17473849
references.citation: Cell. 2007 Oct 5;131(1):174-87
references.pmid: 17923096
references.citation: Cold Spring Harb Perspect Biol. 2011 Jan 01;3(1):a003756
references.pmid: 20573714
references.citation: Annu Rev Biochem. 2012;81:119-43
references.pmid: 22404626
references.citation: Cell. 2013 Feb 28;152(5):1173-83
references.pmid: 23452860
references.citation: Nat Struct Mol Biol. 2007 Feb;14(2):103-5
references.pmid: 17277804
references.citation: Nature. 2010 Jun 24;465(7301):1033-8
references.pmid: 20577206
references.citation: Nature. 2010 Apr 15;464(7291):1071-6
references.pmid: 20393566
references.citation: Cell. 2010 Aug 6;142(3):409-19
references.pmid: 20673990
references.citation: Methods. 2012 Oct;58(2):81-7
references.pmid: 22813890
references.citation: Nature. 2008 Jul 3;454(7200):126-30
references.pmid: 18509338
references.citation: Nature. 2014 Jan 30;505(7485):696-700
references.pmid: 24270811
references.citation: Nature. 2001 Feb 15;409(6822):860-921
references.pmid: 11237011
references.citation: Nature. 2010 Dec 2;468(7324):664-8
references.pmid: 20881964