title: RNA granules: the good, the bad and the ugly.
abstract: Processing bodies (PBs) and Stress Granules (SGs) are the founding members of a new class of RNA granules, known as mRNA silencing foci, as they harbour transcripts circumstantially excluded from the translationally active pool. PBs and SGs are able to release mRNAs thus allowing their translation. PBs are constitutive, but respond to stimuli that affect mRNA translation and decay, whereas SGs are specifically induced upon cellular stress, which triggers a global translational silencing by several pathways, including phosphorylation of the key translation initiation factor eIF2alpha, and tRNA cleavage among others. PBs and SGs with different compositions may coexist in a single cell. These macromolecular aggregates are highly conserved through evolution, from unicellular organisms to vertebrate neurons. Their dynamics is regulated by several signaling pathways, and depends on microfilaments and microtubules, and the cognate molecular motors myosin, dynein, and kinesin. SGs share features with aggresomes and related aggregates of unfolded proteins frequently present in neurodegenerative diseases, and may play a role in the pathology. Virus infections may induce or impair SG formation. Besides being important for mRNA regulation upon stress, SGs modulate the signaling balancing apoptosis and cell survival. Finally, the formation of Nuclear Stress Bodies (nSBs), which share components with SGs, and the assembly of additional cytosolic aggregates containing RNA -the UV granules and the Ire1 foci-, all of them induced by specific cell damage factors, contribute to cell survival.
authors.affiliation: Instituto Leloir, Av. Patricias Argentinas 435, C1405 BWE Buenos Aires, Argentina; CONICET, Buenos Aires, Argentina.
authors.forename: María Gabriela
authors.initials: MG
authors.lastname: Thomas
authors.forename: Mariela
authors.initials: M
authors.lastname: Loschi
authors.forename: María Andrea
authors.initials: MA
authors.lastname: Desbats
authors.forename: Graciela Lidia
authors.initials: GL
authors.lastname: Boccaccio
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003594:Cytoplasmic Granules / Q000378:metabolism*; D006801:Humans; D051379:Mice; D014176:Protein Biosynthesis / Q000502:physiology; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D012333:RNA, Messenger
references.citation: EMBO J. 2002 Dec 16;21(24):6915-24
references.pmid: 12486012
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10804-9
references.pmid: 15249677
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6439-44
references.pmid: 18434538
references.citation: Mol Biol Cell. 2007 Jul;18(7):2592-602
references.pmid: 17475768
references.citation: Exp Cell Res. 2003 Nov 1;290(2):227-33
references.pmid: 14567982
references.citation: FEBS Lett. 2009 Jan 22;583(2):437-42
references.pmid: 19114040
references.citation: Nature. 2005 Aug 25;436(7054):1166-73
references.pmid: 16121183
references.citation: J Cell Biol. 1997 Feb 24;136(4):761-73
references.pmid: 9049243
references.citation: Cell Cycle. 2009 Nov 1;8(21):3462-8
references.pmid: 19823042
references.citation: Nature. 2009 Feb 5;457(7230):687-93
references.pmid: 19079236
references.citation: Mol Biol Cell. 2006 Nov;17(11):4645-55
references.pmid: 16914523
references.citation: J Cell Biol. 1999 Dec 27;147(7):1431-42
references.pmid: 10613902
references.citation: J Cell Sci. 2008 Sep 15;121(Pt 18):3002-14
references.pmid: 18713834
references.citation: PLoS Genet. 2010 Jun 24;6(6):e1000994
references.pmid: 20585616
references.citation: Mol Biol Cell. 2010 Jul 1;21(13):2202-16
references.pmid: 20444979
references.citation: Mol Cell. 2009 Dec 25;36(6):932-41
references.pmid: 20064460
references.citation: J Cell Biol. 2009 Feb 9;184(3):423-35
references.pmid: 19188494
references.citation: J Cell Biol. 2009 Aug 10;186(3):323-31
references.pmid: 19651891
references.citation: J Cell Biol. 2003 Mar 17;160(6):823-31
references.pmid: 12642610
references.citation: Science. 2006 Jul 7;313(5783):104-7
references.pmid: 16825573
references.citation: Mol Cell Biol. 1993 Mar;13(3):1392-407
references.pmid: 8441385
references.citation: Nat Rev Mol Cell Biol. 2004 Oct;5(10):827-35
references.pmid: 15459663
references.citation: Neuron. 2002 Oct 24;36(3):338-40
references.pmid: 12408837
references.citation: Curr Biol. 2003 Feb 18;13(4):286-96
references.pmid: 12593794
references.citation: J Neurosci. 2006 Jul 5;26(27):7143-6
references.pmid: 16822969
references.citation: J Biol Chem. 2005 Apr 29;280(17):16925-33
references.pmid: 15684421
references.citation: Mol Biol Cell. 2008 Oct;19(10):4154-66
references.pmid: 18653466
references.citation: Mol Biol Cell. 2009 Jan;20(1):428-37
references.pmid: 19005212
references.citation: J Virol. 2009 Nov;83(21):11090-101
references.pmid: 19710141
references.citation: Nat Cell Biol. 2008 Oct;10(10):1224-31
references.pmid: 18794846
references.citation: FEBS Lett. 2009 Jan 5;583(1):197-201
references.pmid: 19084008
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11655-9
references.pmid: 17595295
references.citation: Cell. 2005 Jan 28;120(2):195-208
references.pmid: 15680326
references.citation: Biochem Biophys Res Commun. 2004 Jan 30;314(1):268-76
references.pmid: 14715275
references.citation: Nucleic Acids Res. 2008 Nov;36(19):6048-55
references.pmid: 18820301
references.citation: J Biol Chem. 2005 Dec 30;280(52):43131-40
references.pmid: 16221671
references.citation: Mol Biol Cell. 2008 Oct;19(10):4469-79
references.pmid: 18632980
references.citation: EMBO J. 2007 Dec 12;26(24):5020-32
references.pmid: 18034160
references.citation: Cell. 2009 Feb 20;136(4):719-30
references.pmid: 19239891
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10147-52
references.pmid: 19502427
references.citation: J Cell Biol. 2007 Nov 5;179(3):437-49
references.pmid: 17984320
references.citation: Am J Physiol Cell Physiol. 2003 Feb;284(2):C273-84
references.pmid: 12388085
references.citation: J Cell Biol. 2007 Nov 5;179(3):485-500
references.pmid: 17984323
references.citation: J Cell Sci. 2009 Nov 1;122(Pt 21):3973-82
references.pmid: 19825938
references.citation: J Neurosci. 2008 Jul 23;28(30):7555-62
references.pmid: 18650333
references.citation: Mol Cell Biol. 1999 Mar;19(3):2212-9
references.pmid: 10022908
references.citation: Biochem Biophys Res Commun. 2006 Dec 22;351(3):602-11
references.pmid: 17084815
references.citation: Mol Biochem Parasitol. 2010 Jun;171(2):64-73
references.pmid: 20156490
references.citation: Cell Microbiol. 2007 Sep;9(9):2218-29
references.pmid: 17490409
references.citation: Cold Spring Harb Perspect Biol. 2010 Jun;2(6):a000695
references.pmid: 20516127
references.citation: Mol Cell Biol. 2007 Oct;27(19):6639-46
references.pmid: 17664278
references.citation: PLoS One. 2010 Apr 01;5(4):e9942
references.pmid: 20376341
references.citation: J Cell Biol. 1999 Sep 20;146(6):1239-54
references.pmid: 10491388
references.citation: Mol Biol Cell. 2002 May;13(5):1626-40
references.pmid: 12006658
references.citation: Plant Cell. 2006 Dec;18(12):3386-98
references.pmid: 17158604
references.citation: Neuroscience. 2007 May 11;146(2):562-72
references.pmid: 17346899
references.citation: Neuron. 2009 Jan 15;61(1):10-26
references.pmid: 19146809
references.citation: Biochem Soc Trans. 2006 Feb;34(Pt 1):7-11
references.pmid: 16246168
references.citation: J Cell Biol. 2005 Sep 12;170(6):925-34
references.pmid: 16157703
references.citation: J Cell Biol. 2004 Jan 5;164(1):25-33
references.pmid: 14699086
references.citation: Cell Cycle. 2006 Apr;5(7):678-80
references.pmid: 16582624
references.citation: J Biol Chem. 2010 Apr 2;285(14):10959-68
references.pmid: 20129916
references.citation: J Cell Biol. 2007 Oct 8;179(1):65-74
references.pmid: 17908917
references.citation: Mol Cell Biol. 2006 Dec;26(23):8803-13
references.pmid: 16982678
references.citation: RNA. 2008 Oct;14(10):2095-103
references.pmid: 18719243
references.citation: RNA. 2008 Mar;14(3):491-502
references.pmid: 18218704
references.citation: Mol Biol Cell. 2007 Apr;18(4):1385-96
references.pmid: 17392519
references.citation: J Cell Biol. 2010 May 3;189(3):497-510
references.pmid: 20439999
references.citation: J Cell Biol. 2010 May 31;189(5):813-27
references.pmid: 20513766
references.citation: Mol Cell Biol. 2006 Apr;26(7):2716-27
references.pmid: 16537914
references.citation: J Cell Biol. 2009 Apr 6;185(1):43-50
references.pmid: 19332891
references.citation: Neuron. 1997 Jan;18(1):9-12
references.pmid: 9010200
references.citation: Trends Neurosci. 1999 May;22(5):194-7
references.pmid: 10322490
references.citation: Curr Biol. 2006 Dec 5;16(23):2345-51
references.pmid: 17141617
references.citation: Mol Biol Cell. 2005 Jan;16(1):405-20
references.pmid: 15525674
references.citation: Nucleic Acids Res. 2008 May;36(8):2677-89
references.pmid: 18346967
references.citation: J Cell Biol. 2006 Nov 20;175(4):527-34
references.pmid: 17101699
references.citation: J Cell Sci. 2008 Aug 1;121(Pt 15):2463-72
references.pmid: 18611963
references.citation: Genes Dev. 2000 Jun 15;14(12):1460-70
references.pmid: 10859165
references.citation: J Biol Chem. 2005 Dec 30;280(52):42744-9
references.pmid: 16272149
references.citation: EMBO J. 2004 Mar 24;23(6):1313-24
references.pmid: 15014438
references.citation: Biochim Biophys Acta. 2008 Mar;1783(3):479-91
references.pmid: 18023289
references.citation: J Virol. 2008 Feb;82(3):1496-504
references.pmid: 18032499
references.citation: Mol Biol Cell. 2004 Dec;15(12):5383-98
references.pmid: 15371533
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16374-9
references.pmid: 18922781
references.citation: Mol Biol Cell. 2001 Nov;12(11):3502-14
references.pmid: 11694584
references.citation: Trends Biochem Sci. 2007 Apr;32(4):158-64
references.pmid: 17321138
references.citation: PLoS One. 2009 Jun 15;4(6):e5908
references.pmid: 19526060
references.citation: Cell. 2002 Jan 25;108(2):221-32
references.pmid: 11832212
references.citation: Mol Cell Biol. 2010 Apr;30(8):2006-16
references.pmid: 20154146
references.citation: J Neurosci. 2010 May 12;30(19):6782-92
references.pmid: 20463240
references.citation: Cell. 2006 Jun 16;125(6):1111-24
references.pmid: 16777601
references.citation: FEBS Lett. 2010 Jun 18;584(12):2526-38
references.pmid: 20417205
references.citation: Mol Cell Biol. 2007 Dec;27(24):8600-11
references.pmid: 17923697
references.citation: PLoS One. 2010 Apr 02;5(4):e10006
references.pmid: 20368989
references.citation: Mol Cell Biol. 2005 Mar;25(6):2450-62
references.pmid: 15743837
references.citation: J Cell Biol. 2008 Nov 3;183(3):441-55
references.pmid: 18981231
references.citation: FEBS Lett. 2004 Aug 13;572(1-3):69-74
references.pmid: 15304326
references.citation: J Virol. 2005 Dec;79(24):15388-97
references.pmid: 16306610
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18125-30
references.pmid: 17116888
references.citation: Cell Host Microbe. 2007 Nov 15;2(5):295-305
references.pmid: 18005751
references.citation: J Cell Sci. 2010 Feb 1;123(Pt 3):369-83
references.pmid: 20053637
references.citation: Eukaryot Cell. 2007 Nov;6(11):1979-91
references.pmid: 17873083
references.citation: Biochim Biophys Acta. 2010 Jul;1803(7):865-71
references.pmid: 20362631
references.citation: Cell Host Microbe. 2008 Apr 17;3(4):206-12
references.pmid: 18407064
references.citation: Mol Cell Biol. 2005 Nov;25(21):9520-31
references.pmid: 16227602
references.citation: Mol Biol Cell. 2010 Jan 1;21(1):117-30
references.pmid: 19910486
references.citation: Biochem J. 2007 Dec 15;408(3):335-45
references.pmid: 17705785
references.citation: Curr Opin Neurobiol. 2006 Jun;16(3):265-9
references.pmid: 16707258
references.citation: Science. 2003 May 2;300(5620):805-8
references.pmid: 12730603
references.citation: RNA. 2004 Aug;10(8):1266-76
references.pmid: 15247434
references.citation: J Neurochem. 2009 Nov;111(4):1051-61
references.pmid: 19765185
references.citation: Biochem Soc Trans. 2010 Feb;38(Pt 1):242-51
references.pmid: 20074068
references.citation: Mol Biol Cell. 2007 Jul;18(7):2603-18
references.pmid: 17475769
references.citation: Exp Cell Res. 2009 Feb 1;315(3):542-55
references.pmid: 19073175
references.citation: Science. 2008 Apr 4;320(5872):103-6
references.pmid: 18388293
references.citation: Development. 2010 Aug;137(16):2763-72
references.pmid: 20630947
references.citation: J Cell Sci. 2004 Nov 1;117(Pt 23):5567-78
references.pmid: 15494374
references.citation: J Virol. 2010 Apr;84(7):3654-65
references.pmid: 20106928
references.citation: Neuroscience. 2009 Mar 17;159(2):647-56
references.pmid: 19171178
references.citation: Mol Cell. 2005 Dec 22;20(6):905-15
references.pmid: 16364915
references.citation: Mol Biol Cell. 2002 Jan;13(1):195-210
references.pmid: 11809833
references.citation: Nat Cell Biol. 2008 Nov;10(11):1324-32
references.pmid: 18836437
references.citation: Genes Dev. 2010 Aug 1;24(15):1590-5
references.pmid: 20679393
references.citation: J Virol. 2004 Aug;78(16):8582-92
references.pmid: 15280467
references.citation: J Neurosci. 2008 Dec 17;28(51):13793-804
references.pmid: 19091970
references.citation: J Neurosci. 2006 Jun 14;26(24):6496-508
references.pmid: 16775137
references.citation: Eur J Neurosci. 1999 Jan;11(1):293-304
references.pmid: 9987032
references.citation: EMBO J. 2008 Mar 5;27(5):715-26
references.pmid: 18273060
references.citation: J Cell Biol. 2008 Aug 25;182(4):641-6
references.pmid: 18710928
references.citation: J Biol Chem. 2009 Apr 3;284(14):9489-97
references.pmid: 19158085
references.citation: Cell. 2006 Oct 6;127(1):49-58
references.pmid: 17018276
references.citation: Nucleic Acids Res. 2009 Oct;37(19):6600-12
references.pmid: 19729507
references.citation: Cell. 2007 Apr 6;129(1):195-206
references.pmid: 17418795
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2235-40
references.pmid: 17284590
references.citation: RNA Biol. 2010 Jul-Aug;7(4):412-9
references.pmid: 20523112
references.citation: RNA. 2008 Mar;14(3):425-31
references.pmid: 18174314
references.citation: J Neurosci. 2009 Oct 14;29(41):12776-86
references.pmid: 19828789
references.citation: Nature. 2009 Feb 5;457(7230):736-40
references.pmid: 19079237
references.citation: EMBO J. 2010 Aug 18;29(16):2841-57
references.pmid: 20606625
references.citation: Mol Biol Cell. 2001 May;12(5):1393-407
references.pmid: 11359930
references.citation: RNA. 2010 Apr;16(4):748-61
references.pmid: 20179149
references.citation: Biochemistry. 2003 Jun 3;42(21):6536-44
references.pmid: 12767237
references.citation: J Biol Chem. 2001 Apr 27;276(17):13935-40
references.pmid: 11278723
references.citation: RNA. 2002 Dec;8(12):1489-501
references.pmid: 12515382
references.citation: J Biol Chem. 2010 Jan 1;285(1):608-19
references.pmid: 19887443
references.citation: Neurology. 2005 Aug 9;65(3):420-5
references.pmid: 16087907
references.citation: Cancer Cell. 2004 May;5(5):429-41
references.pmid: 15144951
references.citation: Mol Cell. 2008 Dec 5;32(5):605-15
references.pmid: 19061636
references.citation: Plant Physiol. 2009 May;150(1):378-87
references.pmid: 19261735
references.citation: Curr Opin Cell Biol. 2010 Feb;22(1):112-9
references.pmid: 20022233
references.citation: Mol Cell. 2008 Sep 5;31(5):722-36
references.pmid: 18775331
references.citation: Nucleic Acids Res. 2009 May;37(9):2974-83
references.pmid: 19295135
references.citation: J Biol Chem. 2006 Oct 27;281(43):32870-8
references.pmid: 16951406
references.citation: Mol Biol Cell. 2004 Feb;15(2):543-51
references.pmid: 14617804
references.citation: J Cell Biol. 2005 Jun 20;169(6):871-84
references.pmid: 15967811
references.citation: Neuroscience. 2005;134(4):1223-45
references.pmid: 16055272
references.citation: Nat Rev Mol Cell Biol. 2008 Dec;9(12):971-80
references.pmid: 19023284
references.citation: Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13318-23
references.pmid: 20624952
references.citation: Biochim Biophys Acta. 2009 Nov;1793(11):1728-37
references.pmid: 19733198
references.citation: J Cell Biol. 1989 Nov;109(5):1921-35
references.pmid: 2681223
references.citation: FEBS J. 2010 May;277(9):2109-27
references.pmid: 20412057
references.citation: Hum Mol Genet. 2010 Apr 1;19(7):1314-23
references.pmid: 20064924
references.citation: Nat Rev Mol Cell Biol. 2005 Apr;6(4):318-27
references.pmid: 15803138
references.citation: J Cell Sci. 2002 Aug 15;115(Pt 16):3227-34
references.pmid: 12140254
references.citation: RNA. 2005 Apr;11(4):371-82
references.pmid: 15703442
references.citation: Mol Biol Cell. 2008 Nov;19(11):4980-92
references.pmid: 18768757
references.citation: Trends Biochem Sci. 2008 Mar;33(3):141-50
references.pmid: 18291657
references.citation: J Cell Sci. 2009 Jun 15;122(Pt 12):2078-88
references.pmid: 19470581
references.citation: RNA. 2009 Aug;15(8):1433-42
references.pmid: 19535464
references.citation: Mol Microbiol. 2007 Aug;65(3):655-70
references.pmid: 17635187
references.citation: J Cell Sci. 2005 Mar 1;118(Pt 5):981-92
references.pmid: 15731006
references.citation: J Cell Biol. 2006 Mar 13;172(6):803-8
references.pmid: 16520386
references.citation: Methods Enzymol. 2007;431:61-81
references.pmid: 17923231
references.citation: Proc Natl Acad Sci U S A. 2007 May 22;104(21):9041-6
references.pmid: 17502609
references.citation: Biochem J. 2010 Jul 1;429(1):63-72
references.pmid: 20423325
references.citation: Hum Mol Genet. 2002 Nov 15;11(24):3007-17
references.pmid: 12417522
references.citation: Mol Cell Neurosci. 2010 Jan;43(1):43-50
references.pmid: 19837168
references.citation: Mol Cell Biol. 2007 Mar;27(6):2324-42
references.pmid: 17210633
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21591-6
references.pmid: 19966221
references.citation: Genes Dev. 2007 Dec 15;21(24):3381-94
references.pmid: 18079183
references.citation: RNA. 2009 Oct;15(10):1814-21
references.pmid: 19661161
references.citation: Science. 2005 Oct 21;310(5747):486-9
references.pmid: 16141371
references.citation: Neuron. 2003 Oct 9;40(2):347-59
references.pmid: 14556713
references.citation: J Neurosci. 1999 Jan 1;19(1):288-97
references.pmid: 9870958
references.citation: Hum Mol Genet. 2003 Dec 1;12(23):3087-96
references.pmid: 14532325
references.citation: Genes Dev. 2007 Oct 15;21(20):2558-70
references.pmid: 17901217
references.citation: J Cell Biol. 1998 Dec 28;143(7):1883-98
references.pmid: 9864362
references.citation: RNA. 2008 Oct;14(10):1991-8
references.pmid: 18755833
references.citation: J Cell Sci. 2009 Feb 15;122(Pt 4):563-73
references.pmid: 19193871
references.citation: J Cell Biol. 2009 Apr 6;185(1):35-42
references.pmid: 19332886
references.citation: Nat Rev Mol Cell Biol. 2007 Jan;8(1):9-22
references.pmid: 17183357
references.citation: Science. 2009 Nov 27;326(5957):1212-6
references.pmid: 19965463
references.citation: Mol Biol Cell. 2005 Aug;16(8):3753-63
references.pmid: 15930128
references.citation: Mol Biol Cell. 2009 Jun;20(11):2673-83
references.pmid: 19369421
references.citation: Cell Microbiol. 2008 Dec;10(12):2387-99
references.pmid: 18647172
references.citation: J Virol. 2006 Feb;80(4):2019-33
references.pmid: 16439558
references.citation: RNA. 2005 Dec;11(12):1795-802
references.pmid: 16314453
references.citation: Nat Rev Neurosci. 2005 May;6(5):376-87
references.pmid: 15861180
references.citation: Genes Dev. 2007 Mar 15;21(6):719-35
references.pmid: 17369404
references.citation: Mol Cell Biol. 2008 Sep;28(17):5223-37
references.pmid: 18573886
references.citation: Mol Cell Biol. 2007 Jun;27(11):3970-81
references.pmid: 17403906
references.citation: Cell. 2003 Dec 26;115(7):879-91
references.pmid: 14697205
references.citation: Science. 2006 Oct 6;314(5796):130-3
references.pmid: 17023659
references.citation: Dev Biol. 2008 Oct 15;322(2):276-88
references.pmid: 18708044
references.citation: Dev Biol. 2008 Jun 1;318(1):38-51
references.pmid: 18439994
references.citation: J Cell Sci. 2007 Aug 15;120(Pt 16):2774-84
references.pmid: 17652158
references.citation: J Cell Biol. 2000 Dec 11;151(6):1257-68
references.pmid: 11121440
references.citation: Mol Biol Cell. 2006 Oct;17(10):4212-9
references.pmid: 16870703
references.citation: Cell. 2010 Feb 5;140(3):421-35
references.pmid: 20144764
references.citation: Cell Signal. 2010 Apr;22(4):668-75
references.pmid: 20004716