Functional Diversification of SRSF Protein Kinase to Control Ubiquitin-Dependent Neurodevelopmental Signaling.
Amino Acid Motifs
Amino Acid Sequence
Animals
Cell Nucleus
/ metabolism
Gene Expression Regulation, Developmental
Humans
Intellectual Disability
/ genetics
Male
Mice
Mice, Inbred C57BL
Mouse Embryonic Stem Cells
/ metabolism
Mutation
/ genetics
Nervous System
/ embryology
Neurons
/ metabolism
Phosphorylation
Protein Serine-Threonine Kinases
/ antagonists & inhibitors
Proteolysis
Signal Transduction
Substrate Specificity
Transcription Factors
/ metabolism
Ubiquitin
/ metabolism
Ubiquitin-Protein Ligases
/ metabolism
development
metazoan evolution
neural development
neurodevelopmental disorders
protein kinase
protein phosphorylation
signal transduction
stem cells
transcriptomics
ubiquitin signaling
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
07 12 2020
07 12 2020
Historique:
received:
23
03
2020
revised:
17
08
2020
accepted:
25
09
2020
pubmed:
21
10
2020
medline:
12
3
2021
entrez:
20
10
2020
Statut:
ppublish
Résumé
Conserved protein kinases with core cellular functions have been frequently redeployed during metazoan evolution to regulate specialized developmental processes. The Ser/Arg (SR)-rich splicing factor (SRSF) protein kinase (SRPK), which is implicated in splicing regulation, is one such conserved eukaryotic kinase. Surprisingly, we show that SRPK has acquired the capacity to control a neurodevelopmental ubiquitin signaling pathway. In mammalian embryonic stem cells and cultured neurons, SRPK phosphorylates Ser-Arg motifs in RNF12/RLIM, a key developmental E3 ubiquitin ligase that is mutated in an intellectual disability syndrome. Processive phosphorylation by SRPK stimulates RNF12-dependent ubiquitylation of nuclear transcription factor substrates, thereby acting to restrain a neural gene expression program that is aberrantly expressed in intellectual disability. SRPK family genes are also mutated in intellectual disability disorders, and patient-derived SRPK point mutations impair RNF12 phosphorylation. Our data reveal unappreciated functional diversification of SRPK to regulate ubiquitin signaling that ensures correct regulation of neurodevelopmental gene expression.
Identifiants
pubmed: 33080171
pii: S1534-5807(20)30757-7
doi: 10.1016/j.devcel.2020.09.025
pmc: PMC7725506
pii:
doi:
Substances chimiques
Rex-1 protein, mouse
0
Transcription Factors
0
Ubiquitin
0
Rlim protein, mouse
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Srpk1 protein, mouse
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
629-647.e7Subventions
Organisme : Wellcome Trust
ID : 211209/Z/18/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N000609/1
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
Références
Hum Mol Genet. 2012 Mar 15;21(6):1374-83
pubmed: 22156581
Development. 2015 Nov 1;142(21):3734-45
pubmed: 26395480
Nature. 2015 Mar 12;519(7542):223-8
pubmed: 25533962
J Biol Chem. 2014 Dec 12;289(50):34683-98
pubmed: 25281741
Front Cell Neurosci. 2013 Dec 19;7:269
pubmed: 24391546
J Biol Chem. 2009 Sep 4;284(36):24512-25
pubmed: 19592491
Cell Rep. 2018 May 8;23(6):1599-1611
pubmed: 29742418
Histochem Cell Biol. 2012 Jun;137(6):791-800
pubmed: 22350174
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Dev Biol. 2008 Sep 1;321(1):251-62
pubmed: 18625214
Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16699-704
pubmed: 21940502
Nature. 2014 Jul 3;511(7507):86-9
pubmed: 24870238
Prog Neurobiol. 2011 Mar;93(3):421-43
pubmed: 21219963
Nat Commun. 2016 Feb 08;7:10605
pubmed: 26853712
Development. 2009 Oct;136(19):3267-78
pubmed: 19736322
Dev Biol. 2006 Jan 1;289(1):218-28
pubmed: 16316641
Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10514-9
pubmed: 20498046
PLoS One. 2018 Apr 26;13(4):e0196148
pubmed: 29698431
Nature. 2019 Sep;573(7772):61-68
pubmed: 31435019
Mol Cell. 2008 Mar 14;29(5):563-76
pubmed: 18342604
Science. 1999 Feb 19;283(5405):1152-7
pubmed: 10024239
Cell. 1993 Dec 17;75(6):1061-70
pubmed: 8261509
Genes Dev. 1997 Feb 1;11(3):334-44
pubmed: 9030686
Biochem J. 2009 Jan 1;417(1):15-27
pubmed: 19061484
ACS Chem Biol. 2017 Mar 17;12(3):825-832
pubmed: 28135068
PLoS One. 2016 Jun 09;11(6):e0157022
pubmed: 27280887
Mol Cell. 2017 Sep 7;67(5):812-825.e5
pubmed: 28826672
Exp Ther Med. 2019 May;17(5):3883-3890
pubmed: 31007733
Biochim Biophys Acta. 2007 Aug;1773(8):1311-40
pubmed: 17604854
Cell. 1994 Jun 17;77(6):841-52
pubmed: 7911739
Dev Dyn. 2006 Aug;235(8):2282-9
pubmed: 16804892
Nature. 2012 Apr 29;485(7398):386-90
pubmed: 22596162
J Cell Biol. 1998 Feb 23;140(4):737-50
pubmed: 9472028
Cell Chem Biol. 2018 Apr 19;25(4):460-470.e6
pubmed: 29478907
Development. 2003 Apr;130(7):1391-402
pubmed: 12588854
Genome Biol. 2014;15(12):550
pubmed: 25516281
Sci Rep. 2017 May 31;7(1):2497
pubmed: 28566723
Cell Signal. 2019 Feb;54:130-138
pubmed: 30529759
Cell. 2017 Dec 14;171(7):1545-1558.e18
pubmed: 29153836
RNA. 1995 Sep;1(7):692-706
pubmed: 7585254
PLoS One. 2014 Oct 10;9(10):e109038
pubmed: 25303326
Int J Physiol Pathophysiol Pharmacol. 2011 Sep 30;3(3):223-35
pubmed: 21941613
Nat Struct Mol Biol. 2013 Aug;20(8):982-986
pubmed: 23851457
Cell. 2010 Sep 3;142(5):661-7
pubmed: 20813250
J Biol Chem. 1999 Apr 16;274(16):11125-31
pubmed: 10196197
Stem Cells Dev. 2019 Aug 1;28(15):1004-1014
pubmed: 31215318
Nat Commun. 2017 Dec;8(1):7
pubmed: 28232751
RNA. 2001 Sep;7(9):1284-97
pubmed: 11565750
Bioinformatics. 2007 Jan 15;23(2):257-8
pubmed: 17098774
Development. 2016 Jan 1;143(1):88-100
pubmed: 26552887
Mol Psychiatry. 2016 Jan;21(1):133-48
pubmed: 25644381
Mech Dev. 1999 Dec;89(1-2):179-83
pubmed: 10559495
Nat Struct Mol Biol. 2008 May;15(5):435-43
pubmed: 18425142
Genes Dev. 2005 Sep 1;19(17):2066-77
pubmed: 16140986
Dev Biol. 2005 Aug 1;284(1):233-45
pubmed: 15996652
J Cell Biol. 1999 May 3;145(3):447-55
pubmed: 10225947
PLoS One. 2015 Feb 13;10(2):e0116454
pubmed: 25679214
RNA. 1997 Dec;3(12):1456-67
pubmed: 9404896
Nature. 1997 Apr 24;386(6627):833-8
pubmed: 9126742
Cell. 2011 Sep 30;147(1):132-46
pubmed: 21924763
Cell Stem Cell. 2009 May 8;4(5):403-15
pubmed: 19345177
Mol Cell Proteomics. 2006 Apr;5(4):749-57
pubmed: 16340016
Development. 2010 Jun;137(11):1843-52
pubmed: 20431122
PLoS Genet. 2011 Jan 27;7(1):e1002001
pubmed: 21298085
EMBO Rep. 2017 Jul;18(7):1108-1122
pubmed: 28588073
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10824-8
pubmed: 7526381
Stem Cells. 2009 Dec;27(12):3001-11
pubmed: 19821493
Dev Biol. 2016 Dec 1;420(1):110-119
pubmed: 27713059
PLoS One. 2012;7(4):e35347
pubmed: 22514733
Nature. 1994 Jun 23;369(6482):678-82
pubmed: 8208298
J Biol Chem. 2006 Feb 24;281(8):5008-16
pubmed: 16365040
Cell. 2009 Sep 4;138(5):898-910
pubmed: 19737518
Nature. 2017 Feb 23;542(7642):433-438
pubmed: 28135719
Mol Biol Cell. 2013 Oct;24(19):3085-96
pubmed: 23904271
Nature. 1997 Apr 24;386(6627):838-42
pubmed: 9126743
Nat Commun. 2018 Nov 12;9(1):4752
pubmed: 30420655
Dev Biol. 2010 Nov 15;347(2):258-70
pubmed: 20727876
Bioinformatics. 2019 Apr 15;35(8):1441-1442
pubmed: 30239567
Bone. 2014 May;62:10-21
pubmed: 24491691
Biochem J. 1992 Dec 1;288 ( Pt 2):351-5
pubmed: 1334404
Mol Biol Cell. 2006 Feb;17(2):876-85
pubmed: 16319169
Structure. 2007 Jan;15(1):123-33
pubmed: 17223538
EMBO J. 1996 Jan 15;15(2):265-75
pubmed: 8617202
J Biol Chem. 2016 Mar 25;291(13):7107-18
pubmed: 26826126
J Neurosci. 2012 Nov 28;32(48):17262-72
pubmed: 23197718
Eur J Hum Genet. 2015 Dec;23(12):1652-6
pubmed: 25735484
PLoS One. 2012;7(9):e44903
pubmed: 22984583
Int J Mol Sci. 2019 Dec 11;20(24):
pubmed: 31835735
Development. 2006 Jan;133(1):99-106
pubmed: 16319111
Stem Cells. 2007 Dec;25(12):3133-42
pubmed: 17761753
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Mol Cell. 2012 Jun 8;46(5):650-61
pubmed: 22560923
Nature. 2010 Oct 21;467(7318):977-81
pubmed: 20962847
Am J Hum Genet. 1994 Aug;55(2):372-8
pubmed: 8037214
Development. 2018 Jul 26;145(14):
pubmed: 29980564
J Mol Biol. 2008 Feb 8;376(1):55-68
pubmed: 18155240
Cell. 1996 Dec 13;87(6):1001-14
pubmed: 8978605
Mol Psychiatry. 2019 Nov;24(11):1748-1768
pubmed: 29728705
Cell. 2020 Mar 19;180(6):1212-1227.e14
pubmed: 32169215
Dev Biol. 2005 Apr 15;280(2):373-85
pubmed: 15882579
Dev Dyn. 1997 Oct;210(2):79-86
pubmed: 9337129
Proc Natl Acad Sci U S A. 1999 May 11;96(10):5440-5
pubmed: 10318902
Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11329-33
pubmed: 16840555
Mol Cell Biol. 2004 Aug;24(15):6635-44
pubmed: 15254231
Nat Cell Biol. 2002 May;4(5):E127-30
pubmed: 11988757
Development. 1999 Nov;126(21):4749-62
pubmed: 10518492
Nucleic Acids Res. 2006 Jan 1;34(Database issue):D227-30
pubmed: 16381852
Mol Med Rep. 2018 Apr;17(4):5423-5427
pubmed: 29393463
Hum Mutat. 1999;14(5):394-400
pubmed: 10533065