title: Non-coding RNAs: multi-tasking molecules in the cell.
abstract: In the last years it has become increasingly clear that the mammalian transcriptome is highly complex and includes a large number of small non-coding RNAs (sncRNAs) and long noncoding RNAs (lncRNAs). Here we review the biogenesis pathways of the three classes of sncRNAs, namely short interfering RNAs (siRNAs), microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs). These ncRNAs have been extensively studied and are involved in pathways leading to specific gene silencing and the protection of genomes against virus and transposons, for example. Also, lncRNAs have emerged as pivotal molecules for the transcriptional and post-transcriptional regulation of gene expression which is supported by their tissue-specific expression patterns, subcellular distribution, and developmental regulation. Therefore, we also focus our attention on their role in differentiation and development. SncRNAs and lncRNAs play critical roles in defining DNA methylation patterns, as well as chromatin remodeling thus having a substantial effect in epigenetics. The identification of some overlaps in their biogenesis pathways and functional roles raises the hypothesis that these molecules play concerted functions in vivo, creating complex regulatory networks where cooperation with regulatory proteins is necessary. We also highlighted the implications of biogenesis and gene expression deregulation of sncRNAs and lncRNAs in human diseases like cancer.
authors.affiliation: Health Technology College of Lisbon-Polytechnic Institute of Lisbon, 1990-096 Lisbon, Portugal. anita.gomes@estesl.ipl.pt
authors.forename: Anita Quintal
authors.initials: AQ
authors.lastname: Gomes
authors.forename: Sofia
authors.initials: S
authors.lastname: Nolasco
authors.forename: Helena
authors.initials: H
authors.lastname: Soares
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004330:Drosophila; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D016337:RNA, Catalytic; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering
references.citation: Mol Cell. 2008 May 23;30(4):460-71
references.pmid: 18498749
references.citation: Science. 2008 Dec 19;322(5909):1855-7
references.pmid: 19056939
references.citation: Genome Res. 2008 Sep;18(9):1433-45
references.pmid: 18562676
references.citation: Trends Genet. 2012 Aug;28(8):389-96
references.pmid: 22541732
references.citation: Development. 2010 Aug 1;137(15):2493-9
references.pmid: 20573698
references.citation: Curr Biol. 2007 Apr 3;17(7):637-42
references.pmid: 17363252
references.citation: Mol Cell. 2009 Mar 27;33(6):717-26
references.pmid: 19217333
references.citation: RNA Biol. 2009 Jan-Mar;6(1):43-8
references.pmid: 19098462
references.citation: Br J Cancer. 2013 Jun 25;108(12):2419-25
references.pmid: 23660942
references.citation: Cell. 1983 Dec;35(3 Pt 2):849-57
references.pmid: 6197186
references.citation: Nature. 2005 Feb 17;433(7027):769-73
references.pmid: 15685193
references.citation: Cell. 2012 May 11;149(4):819-31
references.pmid: 22541069
references.citation: J Neurosci. 2008 Dec 31;28(53):14341-6
references.pmid: 19118166
references.citation: Nat Med. 2008 Jul;14(7):723-30
references.pmid: 18587408
references.citation: Genes Dev. 2011 Sep 15;25(18):1915-27
references.pmid: 21890647
references.citation: Cell. 2005 Dec 29;123(7):1279-91
references.pmid: 16377568
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11667-72
references.pmid: 19571010
references.citation: Nature. 2013 Jan 10;493(7431):231-5
references.pmid: 23201690
references.citation: Cell. 2007 Jul 27;130(2):287-97
references.pmid: 17662943
references.citation: Proc Natl Acad Sci U S A. 1991 May 1;88(9):3725-8
references.pmid: 2023922
references.citation: Science. 2005 Sep 2;309(5740):1564-6
references.pmid: 16141073
references.citation: FEMS Microbiol Rev. 1999 Jun;23(3):297-316
references.pmid: 10371035
references.citation: Science. 2011 Jan 7;331(6013):76-9
references.pmid: 21127216
references.citation: Immunity. 2011 Aug 26;35(2):169-81
references.pmid: 21820330
references.citation: Nat Struct Mol Biol. 2008 Apr;15(4):346-53
references.pmid: 18345015
references.citation: Cell. 2010 Aug 6;142(3):409-19
references.pmid: 20673990
references.citation: Nature. 2000 Feb 24;403(6772):901-6
references.pmid: 10706289
references.citation: Arch Histol Cytol. 2004 Nov;67(4):271-84
references.pmid: 15700535
references.citation: Science. 2012 Dec 14;338(6113):1435-9
references.pmid: 23239728
references.citation: Nature. 2007 Jun 14;447(7146):799-816
references.pmid: 17571346
references.citation: Nature. 2009 Dec 10;462(7274):799-802
references.pmid: 20010688
references.citation: Nat Genet. 2008 Jun;40(6):751-60
references.pmid: 18469815
references.citation: Cell. 2010 Oct 1;143(1):46-58
references.pmid: 20887892
references.citation: Science. 2007 Jun 8;316(5830):1484-8
references.pmid: 17510325
references.citation: Nat Cell Biol. 2005 Jul;7(7):719-23
references.pmid: 15937477
references.citation: FEBS Lett. 2000 Feb 25;468(2-3):109-14
references.pmid: 10692568
references.citation: Nat Immunol. 2008 Apr;9(4):405-14
references.pmid: 18327259
references.citation: Clin Sci (Lond). 2011 Aug;121(4):141-58
references.pmid: 21526983
references.citation: Cell. 1985 Dec;43(2 Pt 1):405-13
references.pmid: 3907856
references.citation: Science. 2010 Jun 18;328(5985):1534-9
references.pmid: 20558712
references.citation: Biochim Biophys Acta. 2012 Aug;1826(1):121-8
references.pmid: 22498252
references.citation: Genome Res. 2013 Jan;23(1):23-33
references.pmid: 23034409
references.citation: Science. 2007 Apr 27;316(5824):608-11
references.pmid: 17463290
references.citation: Cell. 2007 Mar 23;128(6):1105-18
references.pmid: 17382880
references.citation: Nature. 2005 Nov 17;438(7066):369-73
references.pmid: 16227973
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1608-13
references.pmid: 18227514
references.citation: Nature. 1998 Nov 26;396(6709):336-42
references.pmid: 9845070
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16230-5
references.pmid: 18852463
references.citation: Science. 1995 Jan 13;267(5195):234-7
references.pmid: 7528943
references.citation: Nucleic Acids Res. 2004 Sep 08;32(16):4776-85
references.pmid: 15356295
references.citation: Nat Genet. 2010 Dec;42(12):1113-7
references.pmid: 21057500
references.citation: Adv Exp Med Biol. 2013;768:97-126
references.pmid: 23224967
references.citation: Cell Mol Life Sci. 1999 Oct 1;56(1-2):22-31
references.pmid: 11213258
references.citation: Genes Dev. 2008 Mar 1;22(5):615-26
references.pmid: 18316478
references.citation: RNA Biol. 2012 Jun;9(6):703-19
references.pmid: 22664915
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2257-61
references.pmid: 16461460
references.citation: Cancer Res. 2013 Feb 1;73(3):1180-9
references.pmid: 23243023
references.citation: Dev Cell. 2003 Aug;5(2):337-50
references.pmid: 12919683
references.citation: Microbiol Rev. 1994 Jun;58(2):233-67
references.pmid: 8078435
references.citation: Trends Genet. 2009 Aug;25(8):344-50
references.pmid: 19596481
references.citation: Physiol Genomics. 2007 Feb 12;28(3):294-300
references.pmid: 17105753
references.citation: Nature. 2010 Oct 28;467(7319):1128-32
references.pmid: 20953170
references.citation: Cell. 2012 Oct 26;151(3):521-32
references.pmid: 23063654
references.citation: Cell. 1993 Dec 3;75(5):843-54
references.pmid: 8252621
references.citation: Annu Rev Genet. 2012;46:1-19
references.pmid: 22905871
references.citation: J Exp Med. 2005 Jul 18;202(2):261-9
references.pmid: 16009718
references.citation: Science. 2005 Sep 2;309(5740):1559-63
references.pmid: 16141072
references.citation: Nature. 2009 Jan 22;457(7228):413-20
references.pmid: 19158787
references.citation: Nat Struct Mol Biol. 2006 Dec;13(12):1102-7
references.pmid: 17128271
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17337-42
references.pmid: 17085592
references.citation: Cell Mol Life Sci. 2012 Sep;69(17):2833-42
references.pmid: 22415323
references.citation: Cell. 2007 Jun 29;129(7):1311-23
references.pmid: 17604720
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5343-8
references.pmid: 18390669
references.citation: Cell. 2005 Mar 11;120(5):623-34
references.pmid: 15766526
references.citation: Science. 2006 Jul 21;313(5785):363-7
references.pmid: 16778019
references.citation: Cell. 2007 Jul 27;130(2):299-308
references.pmid: 17662944
references.citation: Development. 2002 Oct;129(19):4371-86
references.pmid: 12223397
references.citation: Trends Biochem Sci. 2004 Feb;29(2):88-94
references.pmid: 15102435
references.citation: Science. 1992 Jun 5;256(5062):1416-9
references.pmid: 1604315
references.citation: Nature. 2012 Nov 15;491(7424):454-7
references.pmid: 23064229
references.citation: Cell. 2007 Mar 23;128(6):1089-103
references.pmid: 17346786
references.citation: Genome Res. 2006 Jan;16(1):11-9
references.pmid: 16344565
references.citation: J Exp Med. 2005 May 2;201(9):1367-73
references.pmid: 15867090
references.citation: Nature. 2007 Feb 8;445(7128):666-70
references.pmid: 17237763
references.citation: Cancer J. 2012 May-Jun;18(3):262-7
references.pmid: 22647363
references.citation: J Clin Invest. 2012 Nov;122(11):4003-11
references.pmid: 23093777
references.citation: RNA. 2011 May;17(5):792-8
references.pmid: 21398401
references.citation: Science. 2007 Nov 2;318(5851):761-4
references.pmid: 17975059
references.citation: Genes Dev. 2006 Aug 1;20(15):1993-7
references.pmid: 16882976
references.citation: J Exp Med. 2011 Jun 6;208(6):1189-201
references.pmid: 21555486
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9667-72
references.pmid: 17535905
references.citation: Biochim Biophys Acta. 2009 Jun;1792(6):497-505
references.pmid: 19268705
references.citation: PLoS One. 2012;7(3):e33711
references.pmid: 22438986
references.citation: PLoS Genet. 2010 Dec 16;6(12):e1001246
references.pmid: 21179579
references.citation: Cell. 2012 Oct 26;151(3):533-46
references.pmid: 23063653
references.citation: Nature. 2009 Jan 22;457(7228):396-404
references.pmid: 19158785
references.citation: Trends Genet. 2006 Feb;22(2):69-73
references.pmid: 16356584
references.citation: Cell. 2007 Jun 15;129(6):1141-51
references.pmid: 17524464
references.citation: Mol Cell. 2006 Feb 17;21(4):533-42
references.pmid: 16483934
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5781-6
references.pmid: 16574773
references.citation: Nat Genet. 2011 Jun 05;43(7):621-9
references.pmid: 21642992
references.citation: Nat Struct Mol Biol. 2008 Jun;15(6):634-40
references.pmid: 18500353
references.citation: Nature. 2008 May 22;453(7194):534-8
references.pmid: 18404147
references.citation: Leukemia. 2012 Mar;26(3):404-13
references.pmid: 22182919
references.citation: RNA Biol. 2010 Sep-Oct;7(5):582-5
references.pmid: 20930520
references.citation: Cell. 2012 Apr 27;149(3):693-707
references.pmid: 22541438
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):16961-6
references.pmid: 16287976
references.citation: Nature. 1989 Jan 26;337(6205):331-7
references.pmid: 2463488
references.citation: Wiley Interdiscip Rev RNA. 2011 Sep-Oct;2(5):632-46
references.pmid: 21823226
references.citation: Nature. 2011 Feb 10;470(7333):284-8
references.pmid: 21307942
references.citation: Science. 2007 Aug 31;317(5842):1220-4
references.pmid: 17761882
references.citation: Nat Genet. 2011 Feb;43(2):153-8
references.pmid: 21186352
references.citation: Curr Biol. 2009 Dec 29;19(24):2066-76
references.pmid: 20022248
references.citation: Wiley Interdiscip Rev RNA. 2010 Sep-Oct;1(2):202-13
references.pmid: 21935885
references.citation: Science. 2005 Sep 2;309(5740):1570-3
references.pmid: 16141075
references.citation: Neuron. 2010 Feb 11;65(3):373-84
references.pmid: 20159450
references.citation: Biochim Biophys Acta. 2008 Nov;1783(11):2130-6
references.pmid: 18706458
references.citation: RNA. 2011 Jun;17(6):1090-9
references.pmid: 21515829
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: Science. 2004 Jan 30;303(5658):672-6
references.pmid: 14704433
references.citation: Biochem Biophys Res Commun. 2010 May 28;396(2):177-81
references.pmid: 20438699
references.citation: Science. 2004 Aug 27;305(5688):1289-92
references.pmid: 15297624
references.citation: Nature. 2007 May 24;447(7143):399-406
references.pmid: 17522672
references.citation: Mol Cell. 2007 Oct 26;28(2):328-36
references.pmid: 17964270
references.citation: Cell. 2003 Oct 17;115(2):209-16
references.pmid: 14567918
references.citation: Curr Genomics. 2009 Mar;10(1):35-41
references.pmid: 19721809
references.citation: Nature. 2008 Jul 3;454(7200):126-30
references.pmid: 18509338
references.citation: Mol Cell. 2012 Oct 26;48(2):219-30
references.pmid: 22959273
references.citation: Curr Opin Genet Dev. 2011 Apr;21(2):194-8
references.pmid: 21330130
references.citation: Genome Biol. 2010;11(3):R26
references.pmid: 20210993
references.citation: Cell. 2007 Apr 6;129(1):69-82
references.pmid: 17418787
references.citation: Nature. 2007 Jun 14;447(7146):875-8
references.pmid: 17507927
references.citation: Hum Mol Genet. 2008 Jun 1;17(11):1631-40
references.pmid: 18283053
references.citation: Nat Rev Mol Cell Biol. 2006 Aug;7(8):612-6
references.pmid: 16723972
references.citation: Science. 2010 Aug 6;329(5992):689-93
references.pmid: 20616235
references.citation: Development. 2008 Apr;135(7):1201-14
references.pmid: 18287206
references.citation: Science. 2008 Oct 31;322(5902):750-6
references.pmid: 18974356
references.citation: Genes Dev. 2006 Jul 15;20(14):1885-98
references.pmid: 16815998
references.citation: Brief Funct Genomic Proteomic. 2004 Aug;3(2):157-67
references.pmid: 15355597
references.citation: RNA. 2007 Mar;13(3):313-6
references.pmid: 17237358
references.citation: Science. 2007 Mar 16;315(5818):1587-90
references.pmid: 17322028
references.citation: Nature. 2010 Feb 4;463(7281):662-5
references.pmid: 20062045
references.citation: Mol Cell. 2010 Sep 24;39(6):925-38
references.pmid: 20797886
references.citation: Genes Dev. 2008 Aug 1;22(15):2085-92
references.pmid: 18676813
references.citation: Nature. 2010 May 13;465(7295):182-7
references.pmid: 20393465
references.citation: Nature. 2009 Jan 22;457(7228):405-12
references.pmid: 19158786
references.citation: EMBO J. 2009 Jun 17;28(12):1708-19
references.pmid: 19461583
references.citation: RNA. 2012 Nov;18(11):2012-9
references.pmid: 23006623
references.citation: Science. 2002 Sep 20;297(5589):2053-6
references.pmid: 12242443
references.citation: Science. 2011 May 13;332(6031):848-52
references.pmid: 21566194
references.citation: Mol Cell. 2008 Nov 7;32(3):383-93
references.pmid: 18995836
references.citation: Hum Mol Genet. 2006 Apr 15;15 Spec No 1:R17-29
references.pmid: 16651366
references.citation: Nature. 2009 Mar 12;458(7235):223-7
references.pmid: 19182780
references.citation: Genes Dev. 2012 Nov 1;26(21):2361-73
references.pmid: 23124062
references.citation: Science. 1992 Sep 25;257(5078):1918-25
references.pmid: 1411506
references.citation: Nature. 2007 Jun 28;447(7148):1130-4
references.pmid: 17554337
references.citation: Genome Biol. 2005;6(8):R71
references.pmid: 16086853
references.citation: Nat Genet. 2003 Nov;35(3):215-7
references.pmid: 14528307
references.citation: J Biol Chem. 2000 Apr 14;275(15):11507-13
references.pmid: 10753970
references.citation: Mol Cell. 2011 Sep 16;43(6):1040-6
references.pmid: 21925392
references.citation: Cancer Res. 2005 Jul 15;65(14):6029-33
references.pmid: 16024602
references.citation: PLoS One. 2012;7(8):e42536
references.pmid: 22880023
references.citation: Science. 2005 May 6;308(5723):833-8
references.pmid: 15774722
references.citation: J Cell Biochem. 2012 Feb;113(2):373-80
references.pmid: 21928326
references.citation: Cell. 2012 Nov 21;151(5):964-80
references.pmid: 23159368
references.citation: J Theor Biol. 2003 May 7;222(1):127-34
references.pmid: 12699739
references.citation: Nat Chem Biol. 2007 Mar;3(3):166-73
references.pmid: 17259978
references.citation: Nucleic Acids Res. 2009 May;37(9):2984-95
references.pmid: 19304753
references.citation: PLoS Comput Biol. 2009 Jul;5(7):e1000449
references.pmid: 19649160
references.citation: Curr Biol. 2005 Mar 29;15(6):501-12
references.pmid: 15797018
references.citation: Nat Cell Biol. 2012 Nov;14(11):1114-21
references.pmid: 23131918
references.citation: RNA. 2008 Oct;14(10):2030-7
references.pmid: 18820242
references.citation: Nature. 2008 May 22;453(7194):539-43
references.pmid: 18404146
references.citation: Cell Motil Cytoskeleton. 1999;43(3):243-54
references.pmid: 10401580
references.citation: Oncogene. 2006 Oct 9;25(46):6170-5
references.pmid: 17028596
references.citation: Biochem Biophys Res Commun. 2004 Sep 17;322(2):593-600
references.pmid: 15325271
references.citation: Nucleic Acids Res. 2010 Sep;38(17):5797-806
references.pmid: 20460456
references.citation: PLoS Genet. 2012;8(7):e1002797
references.pmid: 22844244
references.citation: Biochimie. 2002 Aug;84(8):775-90
references.pmid: 12457565
references.citation: Nat Struct Mol Biol. 2013 Mar;20(3):300-7
references.pmid: 23463315
references.citation: Nature. 2004 Sep 16;431(7006):343-9
references.pmid: 15372041
references.citation: Science. 2005 Sep 2;309(5740):1573-6
references.pmid: 16081698
references.citation: RNA. 2011 Dec;17(12):2085-93
references.pmid: 22028365
references.citation: Cell. 1981 Dec;27(3 Pt 2):487-96
references.pmid: 6101203
references.citation: J Alzheimers Dis. 2008 May;14(1):27-41
references.pmid: 18525125
references.citation: J Cell Biol. 2010 Nov 29;191(5):905-13
references.pmid: 21115802
references.citation: EMBO J. 1995 Dec 15;14(24):6333-8
references.pmid: 8557053