Tau aggregates are RNA-protein assemblies that mislocalize multiple nuclear speckle components.

Alzheimer Disease / metabolism Animals Cell Nucleus / metabolism Cytosol / metabolism Female HEK293 Cells Humans Male Mice Mice, Inbred C57BL Protein Binding Protein Transport RNA Splicing RNA, Small Nucleolar / metabolism RNA-Binding Proteins / metabolism tau Proteins / metabolism
Alzheimer's Disease Frontemporal Dementia MAPT Nuclear Speckles RNA RNA binding proteins SRRM2 Splicing Tau snRNA

Journal

Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320

Informations de publication

Date de publication:
19 05 2021
Historique:
received: 07 08 2020
revised: 05 02 2021
accepted: 18 03 2021
pubmed: 14 4 2021
medline: 22 6 2021
entrez: 13 4 2021
Statut: ppublish

Résumé

Tau aggregates contribute to neurodegenerative diseases, including frontotemporal dementia and Alzheimer's disease (AD). Although RNA promotes tau aggregation in vitro, whether tau aggregates in cells contain RNA is unknown. We demonstrate, in cell culture and mouse brains, that cytosolic and nuclear tau aggregates contain RNA with enrichment for small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs). Nuclear tau aggregates colocalize with and alter the composition, dynamics, and organization of nuclear speckles, membraneless organelles involved in pre-mRNA splicing. Moreover, several nuclear speckle components, including SRRM2, mislocalize to cytosolic tau aggregates in cells, mouse brains, and brains of individuals with AD, frontotemporal dementia (FTD), and corticobasal degeneration (CBD). Consistent with these alterations, we observe that the presence of tau aggregates is sufficient to alter pre-mRNA splicing. This work identifies tau alteration of nuclear speckles as a feature of tau aggregation that may contribute to the pathology of tau aggregates.

Identifiants

DOI: 10.1016/j.neuron.2021.03.026 PMID: 33848474 PMC: PMC8141031
pubmed: 33848474
pii: S0896-6273(21)00196-3
doi: 10.1016/j.neuron.2021.03.026
pmc: PMC8141031
mid: NIHMS1694315
pii:
doi:

Substances chimiques

RNA, Small Nucleolar 0
RNA-Binding Proteins 0
SRRM2 protein, human 0
tau Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

1675-1691.e9

Subventions

Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIA NIH HHS
ID : F30 AG063468
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG002132
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM045443
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests R.P. is a founder and consultant for Faze Medicines. S.B.P. is a member of the Scientific Advisory Boards of ViewPoint Therapeutics and New Ventures Inc. and a member of the Supervisory Board of Priavoid, none of which have contributed financial or any other support to these studies.

Références

Elife. 2016 Feb 01;5:e11752
pubmed: 26829591
Sci Transl Med. 2019 May 1;11(490):
pubmed: 31043574
RNA. 2009 Dec;15(12):2161-73
pubmed: 19854871
Cell Rep. 2019 Dec 24;29(13):4377-4388.e4
pubmed: 31875547
Proc Natl Acad Sci U S A. 1988 Jun;85(11):4051-5
pubmed: 3131773
J Neurosci. 2005 Oct 5;25(40):9171-5
pubmed: 16207876
Neuron. 2016 Nov 23;92(4):796-812
pubmed: 27974162
Invest Ophthalmol Vis Sci. 2003 Nov;44(11):4715-23
pubmed: 14578391
BMC Genomics. 2020 Feb 6;21(1):128
pubmed: 32028886
Neuron. 2010 Dec 22;68(6):1067-81
pubmed: 21172610
JAMA Neurol. 2019 Aug 01;76(8):915-924
pubmed: 31157827
BMB Rep. 2016 Aug;49(8):405-13
pubmed: 27222125
Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):E4376-85
pubmed: 25261551
Nature. 2018 Sep;561(7721):137-140
pubmed: 30158706
PLoS One. 2013 Dec 30;8(12):e84849
pubmed: 24386422
Nature. 2017 Jul 13;547(7662):185-190
pubmed: 28678775
Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16562-7
pubmed: 24023061
Mol Neurodegener. 2014 Apr 28;9:15
pubmed: 24773620
Brain. 2018 Jul 1;141(7):2194-2212
pubmed: 29733334
Mol Cell. 2017 Nov 16;68(4):808-820.e5
pubmed: 29129640
Trends Pharmacol Sci. 2017 Jul;38(7):637-648
pubmed: 28455089
Elife. 2020 Oct 23;9:
pubmed: 33095160
Mol Cell. 2019 Sep 19;75(6):1203-1217.e5
pubmed: 31494035
Sci Transl Med. 2019 Dec 18;11(523):
pubmed: 31852801
J Endocrinol. 2010 Apr;205(1):25-36
pubmed: 20061514
Sci Rep. 2018 Dec 7;8(1):17702
pubmed: 30531974
Sci Rep. 2019 May 28;9(1):7953
pubmed: 31138886
J Mol Biol. 2019 Feb 15;431(4):873-884
pubmed: 30664870
Mol Psychiatry. 2018 Oct;23(10):2090-2110
pubmed: 30283027
Biomolecules. 2016 Jan 07;6(1):9
pubmed: 26751496
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nat Commun. 2016 Jul 28;7:12338
pubmed: 27465542
Front Cell Neurosci. 2014 Mar 18;8:84
pubmed: 24672431
Genes (Basel). 2010 Jun 03;1(1):70-84
pubmed: 24710011
PLoS Comput Biol. 2007 Oct;3(10):2019-31
pubmed: 17967051
J Neurocytol. 1988 Dec;17(6):827-33
pubmed: 3230400
J Neurosci. 2002 Nov 1;22(21):9340-51
pubmed: 12417659
Mov Disord. 2005 Aug;20 Suppl 12:S45-52
pubmed: 16092090
Acta Neuropathol Commun. 2018 Aug 1;6(1):71
pubmed: 30068389
Ann Neurol. 1997 Feb;41(2):200-9
pubmed: 9029069
Nat Methods. 2019 Dec;16(12):1226-1232
pubmed: 31570887
Neurobiol Aging. 1995 May-Jun;16(3):479-86
pubmed: 7566354
Neurobiol Aging. 1998 Nov-Dec;19(6):535-43
pubmed: 10192212
Am J Pathol. 2000 Apr;156(4):1151-5
pubmed: 10751338
BMC Genomics. 2014 Jul 11;15:583
pubmed: 25012247
Nucleic Acids Res. 2017 Oct 13;45(18):10350-10368
pubmed: 28977640
J Cell Biol. 2004 Mar 15;164(6):843-50
pubmed: 15024032
PLoS Biol. 2017 Jul 6;15(7):e2002183
pubmed: 28683104
Brain Res. 2017 Dec 15;1677:129-137
pubmed: 28974363
J Cell Physiol. 2016 Jun;231(6):1269-75
pubmed: 26496460
FEBS Lett. 1996 Dec 16;399(3):344-9
pubmed: 8985176
Cell Res. 2018 Mar;28(3):307-322
pubmed: 29360106
Neuron. 2014 Jun 18;82(6):1271-88
pubmed: 24857020
Protein Pept Lett. 2006;13(7):679-85
pubmed: 17018010
J Vis Exp. 2017 Oct 24;(128):
pubmed: 29155708
Elife. 2018 Apr 30;7:
pubmed: 29708497
Cell. 2002 Apr 19;109(2):145-8
pubmed: 12007400
Nat Genet. 2018 Nov;50(11):1584-1592
pubmed: 30297968
Nat Neurosci. 2011 Apr;14(4):459-68
pubmed: 21358643
Clin Neuropathol. 1995 Mar-Apr;14(2):100-4
pubmed: 7606894
Cold Spring Harb Perspect Biol. 2011 Feb 01;3(2):
pubmed: 20926517
PLoS Biol. 2018 Jul 3;16(7):e2005970
pubmed: 29969450
PLoS One. 2009 Aug 06;4(8):e6529
pubmed: 19657394
J Cell Biol. 2007 Oct 22;179(2):321-30
pubmed: 17954613
J Neurosci. 2005 Nov 16;25(46):10637-47
pubmed: 16291936
Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):E8187-E8196
pubmed: 27911827
Biochemistry. 2015 Aug 4;54(30):4731-40
pubmed: 26177386
J Neurosci. 2016 Jan 20;36(3):1001-7
pubmed: 26791227
Nat Commun. 2020 Aug 27;11(1):4305
pubmed: 32855391
Cell. 2013 Aug 15;154(4):727-36
pubmed: 23953108
Hum Mol Genet. 2011 May 15;20(10):1989-99
pubmed: 21355046
J Cell Biol. 1994 Aug;126(4):877-99
pubmed: 7519622
Proc Natl Acad Sci U S A. 2017 Dec 19;114(51):E11029-E11036
pubmed: 29203673
Nat Neurosci. 2018 Jan;21(1):72-80
pubmed: 29273772
J Cell Sci. 2008 May 1;121(Pt 9):1526-37
pubmed: 18411249
Mech Ageing Dev. 1984 Jan;24(1):101-17
pubmed: 6141331
Proc Natl Acad Sci U S A. 1988 Jun;85(12):4506-10
pubmed: 3132715
Brain Res Brain Res Rev. 2000 Aug;33(1):95-130
pubmed: 10967355
Nature. 1992 Dec 17;360(6405):674-7
pubmed: 1465130
Biochim Biophys Acta. 2000 Jul 26;1502(1):110-21
pubmed: 10899436
J Cell Sci. 1998 Nov;111 ( Pt 21):3167-77
pubmed: 9763511
Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):E313-21
pubmed: 23269837
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Brain Pathol. 2014 Jul;24(4):344-51
pubmed: 24571648
J Biol Chem. 2012 Jun 8;287(24):20522-33
pubmed: 22496370
RNA. 2017 Oct;23(10):1582-1591
pubmed: 28698239
Cell Rep. 2016 May 17;15(7):1455-1466
pubmed: 27160897
Nat Neurosci. 2012 Nov;15(11):1488-97
pubmed: 23023293
Acta Neuropathol Commun. 2021 Jan 28;9(1):18
pubmed: 33509301
F1000Res. 2018 Aug 24;7:1338
pubmed: 30254741
Mol Cell Proteomics. 2015 Nov;14(11):3000-14
pubmed: 26269332
Acta Neuropathol. 1998 Nov;96(5):487-94
pubmed: 9829812
Neurobiol Dis. 2015 Oct;82:540-551
pubmed: 26385829
Acta Neuropathol. 2019 Feb;137(2):259-277
pubmed: 30465259
Nature. 2016 Nov 10;539(7628):197-206
pubmed: 27830784
J Cell Biol. 2010 Jan 25;188(2):181-90
pubmed: 19951897
Nature. 2020 Apr;580(7802):283-287
pubmed: 32050258
Neuron. 2007 Feb 1;53(3):337-51
pubmed: 17270732
Nature. 2019 Apr;568(7752):420-423
pubmed: 30894745
Cell Rep. 2019 Oct 8;29(2):301-316.e10
pubmed: 31597093
Database (Oxford). 2011 Jul 23;2011:bar030
pubmed: 21785142
Nat Commun. 2017 Aug 17;8(1):275
pubmed: 28819146
J Cell Biol. 1995 Dec;131(5):1327-40
pubmed: 8522593

Auteurs

Evan Lester (E)

Department of Biochemistry, University of Colorado, Boulder, CO, USA; Medical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Felicia K Ooi (FK)

Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.

Nadine Bakkar (N)

Department of Neurobiology, Barrow Neurological Institute, Phoenix, AZ, USA.

Jacob Ayers (J)

Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA; Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.

Amanda L Woerman (AL)

Department of Biology and Institute for Applied Life Sciences, University of Massachusetts Amherst, Amherst, MA, USA.

Joshua Wheeler (J)

Department of Biochemistry, University of Colorado, Boulder, CO, USA; Medical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Pathology, Stanford University, Stanford, CA, USA.

Robert Bowser (R)

Department of Neurobiology, Barrow Neurological Institute, Phoenix, AZ, USA.

George A Carlson (GA)

Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA; Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.

Stanley B Prusiner (SB)

Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA; Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA; Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA.

Roy Parker (R)

Department of Biochemistry, University of Colorado, Boulder, CO, USA; Howard Hughes Medical Institute, University of Colorado, Boulder, CO, USA. Electronic address: roy.parker@colorado.edu.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

Recherchemedicale.com › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Tau aggregates are RNA-protein assemblies that...
Recherchemedicale.com › Eucaryotes › Animaux › Tau aggregates are RNA-protein assemblies that...
Recherchemedicale.com › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Noyau de la cellule › Tau aggregates are RNA-protein assemblies that...
Recherchemedicale.com › Cellules › Structures cellulaires › Fractions subcellulaires › Cytosol › Tau aggregates are RNA-protein assemblies that...
Recherchemedicale.com › Cellules › Cellules épithéliales › Cellules HEK293 › Tau aggregates are RNA-protein assemblies that...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Tau aggregates are RNA-protein assemblies that...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Tau aggregates are RNA-protein assemblies that...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Tau aggregates are RNA-protein assemblies that...
Recherchemedicale.com › Métabolisme › Liaison aux protéines › Tau aggregates are RNA-protein assemblies that...
Recherchemedicale.com › Métabolisme › Transport biologique › Transport des protéines › Tau aggregates are RNA-protein assemblies that...
Recherchemedicale.com › Phénomènes génétiques › Régulation de l'expression des gènes › Maturation post-transcriptionnelle des ARN › Épissage des ARN › Tau aggregates are RNA-protein assemblies that...
Recherchemedicale.com › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › Petit ARN nucléaire › Petit ARN nucléolaire › Tau aggregates are RNA-protein assemblies that...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines de liaison à l'ARN › Tau aggregates are RNA-protein assemblies that...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Protéines tau › Tau aggregates are RNA-protein assemblies that...