TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration.
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative diseases with clinical and pathological overlap. Landmark discoveries of mutations in the transactive response DNA-binding protein (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS/TLS) as causative of ALS and FTLD, combined with the abnormal aggregation of these proteins, have initiated a shifting paradigm for the underlying pathogenesis of multiple neurodegenerative diseases. TDP-43 and FUS/TLS are both RNA/DNA-binding proteins with striking structural and functional similarities. Their association with ALS and other neurodegenerative diseases is redirecting research efforts toward understanding the role of RNA processing regulation in neurodegeneration.
Lagier-Tourenne
Clotilde
C
Department of Cellular and Molecular Medicine, University of California, La Jolla, CA 92093-6070, USA.
Polymenidou
Magdalini
M
Cleveland
Don W
DW
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology*; D001692:Biological Transport; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics / Q000473:pathology*; D006801:Humans; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D034702:RNA-Binding Protein FUS / Q000378:metabolism / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism
D004268:DNA-Binding Proteins; D034702:RNA-Binding Protein FUS
Mamm Genome. 2008 May;19(5):299-305
18592312
J Neurosci. 2010 Jan 13;30(2):639-49
20071528
Acta Neuropathol. 2009 Nov;118(5):629-31
19844730
J Biol Chem. 2009 Mar 20;284(12):8083-92
19112176
Amyotroph Lateral Scler. 2010;11(1-2):240-3
19306141
Neuropathology. 2009 Dec;29(6):689-96
19170893
Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18809-14
19833869
J Neuropathol Exp Neurol. 2008 Dec;67(12):1159-65
19018245
Ann Neurol. 2008 Jul;64(1):60-70
18546284
Brain Res. 2009 Jan 16;1249:202-11
19046946
Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6439-44
18434538
Genes Dev. 2007 Sep 1;21(17):2172-81
17785525
Brain Res. 2007 Dec 12;1184:284-94
17963732
Am J Pathol. 2008 Jul;173(1):182-94
18535185
Acta Neuropathol. 2009 Nov;118(5):633-45
19618195
RNA. 1995 Sep;1(7):724-33
7585257
Acta Neuropathol. 2008 Aug;116(2):169-82
18481073
Neurology. 2009 Aug 18;73(7):511-7
19687452
J Biol Chem. 2009 Mar 27;284(13):8516-24
19164285
Hum Mutat. 2009 Apr;30(4):688-94
19224587
Ann Neurol. 2009 Apr;65(4):470-3
19350673
Acta Neuropathol. 2009 Jan;117(1):45-53
18923836
Genes Dev. 1994 Nov 1;8(21):2513-26
7958914
Parkinsonism Relat Disord. 2009 May;15(4):281-6
18723384
Cancer Res. 2001 May 1;61(9):3586-90
11325824
Hum Mol Genet. 2010 May 1;19(9):1741-55
20147319
BMC Med Genet. 2010 Jan 19;11:8
20082726
J Neurol Neurosurg Psychiatry. 2003 May;74(5):683-6
12700323
Nat Rev Mol Cell Biol. 2009 Feb;10(2):126-39
19165215
J Neuropathol Exp Neurol. 2008 Apr;67(4):271-9
18379440
J Neurol Sci. 2009 Sep 15;284(1-2):69-71
19411082
Acta Neuropathol. 2007 May;113(5):543-8
17415574
Neurology. 2005 Aug 23;65(4):586-90
16116120
FEBS Lett. 2006 Feb 20;580(5):1339-44
16458894
Nat Rev Mol Cell Biol. 2009 Jun;10(6):430-6
19461665
Eur J Neurol. 2009 Jun;16(6):727-32
19236453
Amyotroph Lateral Scler. 2010;11(1-2):223-7
19714537
EMBO J. 2010 Jan 6;29(1):209-21
19910924
Acta Neuropathol. 2009 Feb;117(2):209-11
19066918
J Mol Biol. 2006 Oct 13;363(1):27-38
16965792
Neurosci Lett. 2005 May 13;379(3):152-7
15843054
J Biol Chem. 2008 Jan 18;283(3):1744-1753
17984093
EMBO J. 1998 Aug 3;17(15):4442-55
9687511
EMBO J. 2004 Apr 21;23(8):1782-91
15057275
J Neuropathol Exp Neurol. 2009 Nov;68(11):1167-76
19816201
Mol Cell Neurosci. 2007 Jun;35(2):320-7
17481916
Brain. 2008 May;131(Pt 5):1282-93
18362096
Science. 2009 Feb 27;323(5918):1208-1211
19251628
J Neurochem. 2008 May;105(3):797-806
18088371
Acta Neuropathol. 2009 Sep;118(3):349-58
19455346
EMBO J. 1996 Sep 16;15(18):5022-31
8890175
Nature. 2008 Nov 27;456(7221):464-9
18978773
Neuroscience. 2009 Jan 23;158(2):745-50
19013502
PLoS One. 2008 Jun 11;3(6):e2450
18545701
Neurobiol Aging. 2009 Aug;30(8):1272-5
19450904
Cell. 2008 Jan 11;132(1):27-42
18191218
Brain. 2007 May;130(Pt 5):1386-94
17439983
Mov Disord. 2009 Jan 15;24(1):32-9
19006185
Nucleic Acids Res. 2005 Oct 27;33(18):6000-10
16254078
Neurobiol Aging. 2011 Mar;32(3):550.e1-4
20138404
J Exp Med. 2010 Jan 18;207(1):117-28
20026663
J Biol Chem. 2008 Oct 31;283(44):30289-99
18715868
Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13583-8
12361981
Neuropathol Appl Neurobiol. 2009 Apr;35(2):222-5
18986339
J Biol Chem. 1998 Feb 27;273(9):4838-42
9478924
Acta Neuropathol. 2009 Nov;118(5):617-27
19830439
Acta Neuropathol. 2009 Nov;118(5):719-20
19844732
Biochem Biophys Res Commun. 2006 Dec 22;351(3):602-11
17084815
J Neurol Sci. 2008 Jun 15;269(1-2):30-4
18206910
Mol Brain. 2009 Sep 25;2:30
19781077
Acta Neuropathol. 2008 Aug;116(2):221-2
18521613
Proteomics. 2006 Nov;6(22):5962-72
17106916
J Virol. 1995 Jun;69(6):3584-96
7745706
Eur J Neurol. 2010 May;17(5):754-6
19922450
J Biol Chem. 2005 Nov 11;280(45):37572-84
16157593
Acta Neuropathol. 2010 Mar;119(3):365-74
19876635
Am J Pathol. 2006 Oct;169(4):1343-52
17003490
Acta Neuropathol. 2009 Apr;117(4):429-44
19194716
J Neuropathol Exp Neurol. 2009 Mar;68(3):262-73
19225410
FEBS Lett. 2009 May 19;583(10):1586-92
19379745
J Biol Chem. 2004 Oct 22;279(43):44834-40
15299008
J Neurosci Res. 2010 Mar;88(4):784-97
19798749
Nature. 1993 Jun 17;363(6430):640-4
8510758
Dev Biol. 2006 Jul 15;295(2):781-90
16730344
Neurobiol Aging. 2011 Nov;32(11):2096-9
20031275
Mol Ther. 2009 Apr;17(4):607-13
19223871
Nature. 1993 Mar 4;362(6415):59-62
8446170
J Biol Chem. 1999 Nov 26;274(48):34337-42
10567410
Arch Neurol. 2008 May;65(5):636-41
18474740
Genes Dev. 2000 Jun 15;14(12):1415-29
10859161
J Neuropathol Exp Neurol. 2008 Jun;67(6):555-64
18520774
Neuroscience. 2009 Dec 29;164(4):1565-78
19782731
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3785-9
18305152
Neurosci Lett. 2009 Sep 29;463(1):87-92
19539703
Nat Genet. 2008 May;40(5):572-4
18372902
Curr Biol. 2006 Dec 5;16(23):2345-51
17141617
Genesis. 2010 Jan;48(1):56-62
20014337
Am J Pathol. 2007 Jul;171(1):227-40
17591968
Ann Neurol. 2008 Apr;63(4):535-8
18288693
J Biol Chem. 2008 Mar 7;283(10):6489-500
18167354
Nucleic Acids Res. 2010 Mar;38(4):1353-66
19965769
Nature. 2007 Jun 14;447(7146):859-63
17568747
J Biol Chem. 2001 Sep 28;276(39):36337-43
11470789
Autophagy. 2010 Feb;6(2):217-27
20104022
Acta Neurol Scand. 2010 Nov;122(5):367-72
20175762
J Neurosci. 2007 Sep 26;27(39):10530-4
17898224
Neurobiol Aging. 2009 Aug;30(8):1329-31
18068872
Neurology. 1998 Dec;51(6):1546-54
9855500
Acta Neuropathol. 2009 Sep;118(3):407-13
19557423
Cell. 2004 May 28;117(5):649-62
15163412
J Orthop Res. 2002 Jul;20(4):723-9
12168660
Mol Cell Biol. 2000 May;20(10):3345-54
10779324
J Biol Chem. 2009 Oct 2;284(40):27416-24
19651785
Cell. 2003 Dec 12;115(6):727-38
14675537
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3858-63
20133711
Nat Genet. 1993 Jun;4(2):175-80
7503811
Mol Biol Cell. 2004 Dec;15(12):5383-98
15371533
Acta Neuropathol. 2008 Aug;116(2):159-67
18553091
Annu Rev Neurosci. 2003;26:267-98
12704221
Science. 2008 Mar 21;319(5870):1668-72
18309045
Neurology. 2010 Feb 2;74(5):366-71
20124201
Mol Cell Biol. 2007 Sep;27(18):6469-83
17562864
Mov Disord. 2009 Sep 15;24(12):1843-7
19609911
Acta Neuropathol. 2009 Sep;118(3):359-69
19330339
Acta Neuropathol. 2009 Oct;118(4):553-60
19526244
Biochem Soc Trans. 2010 Feb;38(Pt 1):150-5
20074050
J Biol Chem. 2001 Mar 2;276(9):6807-16
11098054
Nature. 2006 Jun 15;441(7095):880-4
16625205
J Neurol Neurosurg Psychiatry. 2009 Mar;80(3):354-5
19228676
Anal Chem. 2003 Jul 1;75(13):3107-14
12964758
Nat Genet. 2004 Apr;36(4):377-81
15034582
Neurology. 2009 Oct 13;73(15):1176-9
19741216
J Neuropathol Exp Neurol. 2007 Feb;66(2):152-7
17279000
J Proteome Res. 2010 Feb 5;9(2):1104-20
20020773
Acta Neuropathol. 2007 May;113(5):535-42
17333220
Neurology. 2008 May 6;70(19 Pt 2):1850-7
18401022
Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16719-24
12477934
Front Biosci. 2008 Jan 01;13:867-78
17981595
Neuropathology. 2010 Apr;30(2):170-81
20102522
Brain. 2009 Nov;132(Pt 11):2922-31
19674978
J Cell Sci. 1997 Aug;110 ( Pt 15):1741-50
9264461
Expert Opin Biol Ther. 2008 Jul;8(7):969-78
18549326
Science. 2009 Feb 27;323(5918):1205-8
19251627
J Mol Cell Biol. 2009 Dec;1(2):82-92
19783543
Mol Cell. 2006 Jun 23;22(6):713-717
16793541
Gene. 1998 Oct 23;221(2):191-8
9795213
Neuromuscul Disord. 2009 Oct;19(10):696-700
19695877
Nature. 2006 Jun 15;441(7095):885-9
16625204
J Neurochem. 2009 Aug;110(3):1082-94
19522733
Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3169-74
20133767
Neurology. 2008 Jan 8;70(2):144-52
18180444
Brain Pathol. 2010 Mar;20(2):351-60
19338576
J Neurol Neurosurg Psychiatry. 2009 Nov;80(11):1286-8
19864664
Mol Cell Biol. 1998 Mar;18(3):1489-97
9488465
Nat Neurosci. 2000 Jul;3(7):661-9
10862698
Oncogene. 1994 Dec;9(12):3717-29
7970732
Exp Cell Res. 2003 Feb 15;283(2):184-95
12581738
J Cell Sci. 2008 Nov 15;121(Pt 22):3778-85
18957508
Hum Mol Genet. 2010 Jan 15;19(2):313-28
19864493
Ann Neurol. 2008 Apr;63(4):538-42
18438952
Ann Neurol. 2007 May;61(5):435-45
17469117
J Neurol Sci. 2010 Feb 15;289(1-2):149-54
19732908
J Neural Transm (Vienna). 2008 Dec;115(12):1661-71
18974920
J Neuropathol Exp Neurol. 2007 Mar;66(3):177-83
17356379
J Neurochem. 2009 Nov;111(4):1051-61
19765185
J Biol Chem. 2008 Oct 24;283(43):28852-9
18703504
Acta Neuropathol. 2008 Jan;115(1):123-31
18004574
Ann Neurol. 1993 Feb;33(2):200-7
8257465
Acta Neuropathol. 2008 Aug;116(2):193-203
18560845
Nucleic Acids Symp Ser (Oxf). 2008;(52):213-4
18776329
J Biol Chem. 2009 Aug 14;284(33):22059-22066
19535326
J Cell Biol. 2009 Dec 14;187(6):875-88
20008565
BMC Neurosci. 2008 Oct 28;9:104
18957104
EMBO J. 2001 Apr 2;20(7):1785-96
11285241
J Neurol Neurosurg Psychiatry. 2008 Oct;79(10):1186-9
18796596
Neurology. 2002 Oct 8;59(7):1077-9
12370467
Genomics. 2004 Jan;83(1):130-9
14667816
BMC Cell Biol. 2008 Jul 11;9:37
18620564
Nature. 2004 Feb 26;427(6977):801
14985749
EMBO J. 2001 Apr 2;20(7):1774-84
11285240
J Cell Biol. 2009 Dec 14;187(6):761-72
19951898
Acta Neuropathol. 2007 Jul;114(1):71-9
17569066
EMBO J. 2006 Jul 26;25(14):3357-66
16810319
Genomics. 1996 Oct 1;37(1):1-8
8921363
J Neurol Neurosurg Psychiatry. 2010 Jun;81(6):639-45
19965854
Neuron. 1998 Mar;20(3):589-602
9539131
Brief Funct Genomic Proteomic. 2006 Mar;5(1):8-14
16769671
Neurosci Res. 2010 Jan;66(1):131-3
19833157
J Hum Genet. 2010 Apr;55(4):252-4
20224596
Nat Rev Neurosci. 2006 Sep;7(9):710-23
16924260
Nature. 2002 Sep 12;419(6903):182-5
12226669
Neuron. 2004 Aug 19;43(4):513-25
15312650
Acta Neuropathol. 2007 Jul;114(1):5-22
17579875
J Neurochem. 2009 Sep;110(5):1457-68
19558455
Acta Neuropathol. 2009 Oct;118(4):561-73
19449021
Acta Neuropathol. 2007 Sep;114(3):221-9
17653732
Acta Neuropathol. 2008 Jan;115(1):133-45
17713769
EMBO J. 1997 Jul 16;16(14):4421-32
9250686
Neurosci Lett. 2010 Jan 18;469(1):112-6
19944744
Neuron. 2006 Oct 5;52(1):39-59
17015226
J Neurol Sci. 2000 Nov 1;180(1-2):15-20
11090859
J Biol Chem. 2010 Apr 9;285(15):11068-72
20154090
J Neurol Neurosurg Psychiatry. 2009 Nov;80(11):1283-5
19864663
Acta Neuropathol. 2009 Jan;117(1):15-8
19015862
Cell Mol Neurobiol. 2010 May;30(4):641-52
20043239
Oncogene. 1997 Jan 30;14(4):451-61
9053842
J Biol Chem. 2007 Dec 14;282(50):36143-54
17932037
Nucleic Acids Res. 2009 Jul;37(12):4116-26
19429692
Nat Struct Mol Biol. 2009 Feb;16(2):130-7
19136955
Schizophr Res. 2009 Mar;108(1-3):297-8
18829261
J Biol Chem. 2010 Jan 1;285(1):608-19
19887443
Acta Neuropathol. 2010 Mar;119(3):355-64
19967541
Nature. 2008 Jul 3;454(7200):126-30
18509338
Muscle Nerve. 2009 Jul;40(1):19-31
19533646
Neuropathol Appl Neurobiol. 2008 Aug;34(4):446-56
18657254
Arch Neurol. 2008 Sep;65(9):1185-9
18779421
J Neuropathol Exp Neurol. 2007 Oct;66(10):884-91
17917582
Brain. 2007 May;130(Pt 5):1375-85
17360763
Acta Neuropathol. 2007 May;113(5):521-33
17219193
J Struct Biol. 2009 Sep;167(3):235-41
19539030
Mol Cell Biol. 2010 Jan;30(1):186-96
19841068
Neurosci Lett. 2007 Jun 13;420(2):128-32
17543992
Neuropathology. 2009 Aug;29(4):466-71
18715271
Nature. 2006 Aug 24;442(7105):916-9
16862116
Gastroenterology. 2005 Oct;129(4):1225-36
16230076
PLoS Genet. 2010 Mar 26;6(3):e1000887
20361056
Acta Neuropathol. 2010 Jan;119(1):1-4
19924424
Acta Neuropathol. 2007 Oct;114(4):335-45
17639426
J Cell Sci. 2005 Dec 15;118(Pt 24):5755-65
16317045
Neurobiol Aging. 2011 Mar;32(3):548.e1-4
20018407
Nature. 2006 Aug 24;442(7105):920-4
16862115
Neurology. 2009 Oct 13;73(15):1180-5
19741215
Mol Endocrinol. 1998 Jan;12(1):4-18
9440806
Hum Mutat. 2010 May;31(5):E1377-89
20232451
Brain. 2007 May;130(Pt 5):1360-74
17439980
Neurogenetics. 2010 May;11(2):217-25
19760257
J Med Genet. 2010 Mar;47(3):190-4
19861302
Trends Mol Med. 2008 Nov;14(11):479-85
18929508
J Biol Chem. 2009 Jul 24;284(30):20329-39
19465477
Brain Pathol. 2010 May;20(3):589-97
19832837
J Neurol. 2010 May;257(5):747-53
19946779
Acta Neuropathol. 2008 Dec;116(6):625-37
18843496
Hum Mol Genet. 2009 Sep 15;18(18):3353-64
19515851
Acta Neuropathol. 2008 Aug;116(2):205-13
18607609
Acta Neuropathol. 2008 Aug;116(2):147-57
18536926
J Biol Chem. 2001 Apr 20;276(16):13395-401
11278855
Arch Neurol. 2010 Feb;67(2):224-30
20142531
Curr Biol. 2005 Mar 29;15(6):587-93
15797031
J Mol Biol. 2005 May 6;348(3):575-88
15826655
Nature. 2004 Nov 11;432(7014):235-40
15531877
Nucleic Acids Symp Ser (Oxf). 2009;(53):247-8
19749353
Acta Neuropathol. 2009 Aug;118(2):303-11
19283396
Neurology. 2009 May 12;72(19):1669-76
19433740
J Biol Chem. 2010 Feb 26;285(9):6826-34
20040602
J Am Chem Soc. 2010 Feb 3;132(4):1186-7
20055380
Nat Genet. 2009 Feb;41(2):163-5
19136952
Lancet Neurol. 2008 May;7(5):409-16
18396105
Ann Neurol. 2007 May;61(5):427-34
17469116
Oncogene. 1999 Dec 23;18(56):8000-10
10637511
Hum Mutat. 2009 Nov;30(11):E974-83
19655382
Acta Neuropathol. 2009 Feb;117(2):125-36
19139911
Acta Neuropathol. 2009 Feb;117(2):151-8
19039597
Oncogene. 1999 Aug 5;18(31):4515-21
10442642
PLoS One. 2008 Aug 13;3(8):e2926
18698352
Hum Mol Genet. 2010 Feb 15;19(4):671-83
19959528
EMBO J. 2000 Feb 1;19(3):453-62
10654943
Cell Signal. 2004 Apr;16(4):515-20
14709340
Neuropathology. 2009 Oct;29(5):566-73
19422539
Nat Genet. 2000 Feb;24(2):175-9
10655065
Neuromuscul Disord. 2009 Nov;19(11):766-72
19828315
FEBS Lett. 2008 Aug 20;582(19):2899-904
18656473
Int J Mol Sci. 2009 Jan;10(1):232-246
19333444
J Biol Chem. 2008 May 9;283(19):13302-9
18305110
Acta Neuropathol. 2009 Nov;118(5):605-16
19669651
PLoS Genet. 2008 Sep 19;4(9):e1000193
18802454
EMBO J. 2010 Mar 3;29(5):969-80
20075865
Brain Res. 2009 Nov 3;1296:176-86
19619516
BMC Neurol. 2008 Aug 29;8:32
18755042
Science. 2006 Oct 6;314(5796):130-3
17023659
Mol Cell Proteomics. 2006 Apr;5(4):635-51
16352523
Nucleic Acids Res. 2009 Apr;37(6):1799-808
19174564
Neuropathology. 2009 Dec;29(6):672-83
19496940
Exp Cell Res. 2002 Aug 15;278(2):125-32
12169268
Proc Natl Acad Sci U S A. 2009 May 5;106(18):7607-12
19383787
Genome Res. 2002 Aug;12(8):1231-45
12176931
Neurosci Lett. 2009 Jan 30;450(2):163-6
19103256
Acta Neuropathol. 2009 Feb;117(2):137-49
19125255
Arch Neurol. 2009 Dec;66(12):1483-8
20008652
Biochem J. 2008 Oct 15;415(2):297-307
18620545
J Med Genet. 2009 Feb;46(2):112-4
18931000
Curr Alzheimer Res. 2006 Dec;3(5):485-91
17168647
Acta Neuropathol. 2008 Aug;116(2):215-20
18592255
J Neuropathol Exp Neurol. 2008 Jan;67(1):62-7
18091558
Intern Med. 2010;49(4):331-4
20154440
Acta Neuropathol. 2010 Apr;119(4):409-19
20198480