Nopp140-chaperoned 2'-O-methylation of small nuclear RNAs in Cajal bodies ensures splicing fidelity.
Casein Kinase II
/ antagonists & inhibitors
Cholangiocarcinoma
/ drug therapy
Hematologic Neoplasms
/ drug therapy
Humans
Interstitial Cells of Cajal
/ metabolism
Methylation
Nuclear Proteins
/ metabolism
Phosphoproteins
/ metabolism
Phosphorylation
RNA Splicing
RNA, Small Nuclear
/ chemistry
Ribonucleoproteins
/ metabolism
Spliceosomes
/ genetics
COVID-19 Drug Treatment
Cajal bodies
RNA modification
casein kinase 2
nuclear organization
phosphorylation
pre-mRNA splicing
scaRNPs
snRNA
snoRNPs
Journal
Genes & development
ISSN: 1549-5477
Titre abrégé: Genes Dev
Pays: United States
ID NLM: 8711660
Informations de publication
Date de publication:
01 08 2021
01 08 2021
Historique:
received:
11
05
2021
accepted:
29
06
2021
pubmed:
25
7
2021
medline:
10
8
2021
entrez:
24
7
2021
Statut:
ppublish
Résumé
Spliceosomal small nuclear RNAs (snRNAs) are modified by small Cajal body (CB)-specific ribonucleoproteins (scaRNPs) to ensure snRNP biogenesis and pre-mRNA splicing. However, the function and subcellular site of snRNA modification are largely unknown. We show that CB localization of the protein Nopp140 is essential for concentration of scaRNPs in that nuclear condensate; and that phosphorylation by casein kinase 2 (CK2) at ∼80 serines targets Nopp140 to CBs. Transiting through CBs, snRNAs are apparently modified by scaRNPs. Indeed, Nopp140 knockdown-mediated release of scaRNPs from CBs severely compromises 2'-O-methylation of spliceosomal snRNAs, identifying CBs as the site of scaRNP catalysis. Additionally, alternative splicing patterns change indicating that these modifications in U1, U2, U5, and U12 snRNAs safeguard splicing fidelity. Given the importance of CK2 in this pathway, compromised splicing could underlie the mode of action of small molecule CK2 inhibitors currently considered for therapy in cholangiocarcinoma, hematological malignancies, and COVID-19.
Identifiants
pubmed: 34301768
pii: gad.348660.121
doi: 10.1101/gad.348660.121
pmc: PMC8336889
doi:
Substances chimiques
NOLC1 protein, human
0
Nuclear Proteins
0
Phosphoproteins
0
RNA, Small Nuclear
0
Ribonucleoproteins
0
Casein Kinase II
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1123-1141Subventions
Organisme : NCI NIH HHS
ID : P30 CA013330
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM033397
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136662
Pays : United States
Organisme : NIH HHS
ID : S10 OD016214
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2021 Bizarro et al.; Published by Cold Spring Harbor Laboratory Press.
Références
Nat Biotechnol. 2010 May;28(5):511-5
pubmed: 20436464
Mol Biol Cell. 2007 Jun;18(6):2296-304
pubmed: 17429075
Nucleic Acids Res. 2012 Nov 1;40(20):e157
pubmed: 22833606
Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):12934-12939
pubmed: 29158377
RNA. 2004 Dec;10(12):1925-33
pubmed: 15525712
Chromosoma. 2015 Jun;124(2):191-208
pubmed: 25384888
Nucleic Acids Res. 2018 Oct 12;46(18):9289-9298
pubmed: 30202881
J Cell Biol. 1990 Dec;111(6 Pt 1):2235-45
pubmed: 2177472
EMBO J. 2016 Mar 15;35(6):654-67
pubmed: 26873591
Int J Mol Sci. 2018 Jan 27;19(2):
pubmed: 29382046
Mol Biol Cell. 2009 Dec;20(24):5250-9
pubmed: 19846657
Biochem J. 2009 Jul 15;421(3):387-95
pubmed: 19432557
Cancer Res. 2010 Dec 15;70(24):10288-98
pubmed: 21159648
Mol Cell Biol. 1999 Oct;19(10):6906-17
pubmed: 10490628
Angew Chem Int Ed Engl. 2015 Jan 7;54(2):451-5
pubmed: 25417815
Nucleic Acids Res. 2020 Nov 4;48(19):e110
pubmed: 32976574
Annu Rev Biochem. 2020 Jun 20;89:359-388
pubmed: 31794245
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Biochimie. 1995;77(1-2):22-9
pubmed: 7599273
Cell. 1997 May 30;89(5):669-72
pubmed: 9182752
Methods Enzymol. 2000;318:493-506
pubmed: 10890008
Science. 2020 Dec 18;370(6523):
pubmed: 33243851
Org Biomol Chem. 2017 Oct 31;15(42):8872-8876
pubmed: 29048444
Mol Biol Cell. 1992 May;3(5):555-69
pubmed: 1535243
Mol Cell. 2013 Aug 22;51(4):539-51
pubmed: 23973377
Nucleic Acids Res. 2007;35(2):550-8
pubmed: 17169984
Genes Dev. 1989 Dec;3(12B):2124-36
pubmed: 2560754
Chromosoma. 2005 May;114(1):1-14
pubmed: 15770508
Nat Rev Mol Cell Biol. 2003 Dec;4(12):975-80
pubmed: 14685175
EMBO J. 2001 Jul 16;20(14):3617-22
pubmed: 11447102
J Biol Chem. 1996 Aug 9;271(32):19376-84
pubmed: 8702624
RNA. 2004 Apr;10(4):681-90
pubmed: 15037777
Cell. 1992 Jul 10;70(1):127-38
pubmed: 1623516
Nucleic Acids Res. 2016 Sep 19;44(16):e135
pubmed: 27302133
Mol Biol Cell. 2019 Dec 15;30(26):3136-3150
pubmed: 31664887
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Biochem J. 2001 Jun 1;356(Pt 2):297-310
pubmed: 11368755
J Cell Biol. 1984 Aug;99(2):672-9
pubmed: 6204996
RNA. 1997 Mar;3(3):324-31
pubmed: 9056769
J Cell Biol. 2001 Jul 23;154(2):293-307
pubmed: 11470819
Genome Biol. 2014;15(12):550
pubmed: 25516281
RNA. 2012 Jan;18(1):31-6
pubmed: 22124016
Nucleic Acids Res. 2006 Jan 1;34(Database issue):D158-62
pubmed: 16381836
J Cell Sci. 2004 Dec 1;117(Pt 25):5949-51
pubmed: 15564372
Cell. 2017 May 18;169(5):918-929.e14
pubmed: 28502770
Science. 2015 Nov 27;350(6264):1096-101
pubmed: 26472758
J Histochem Cytochem. 1990 Sep;38(9):1237-56
pubmed: 2201735
Nucleic Acids Res. 2015 Feb 27;43(4):2242-58
pubmed: 25653167
Mol Cell. 2020 Mar 5;77(5):1014-1031.e13
pubmed: 32017898
RNA Biol. 2017 Jun 3;14(6):680-692
pubmed: 27715451
RNA. 1997 Sep;3(9):950-1
pubmed: 9292493
Annu Rev Biochem. 1995;64:897-934
pubmed: 7574504
Curr Opin Cell Biol. 1999 Jun;11(3):385-90
pubmed: 10395554
Biochim Biophys Acta. 2013 Jan;1834(1):342-50
pubmed: 22906532
RNA Biol. 2017 Jun 3;14(6):669-670
pubmed: 28486008
EMBO J. 2003 Apr 15;22(8):1878-88
pubmed: 12682020
Cell. 2020 Aug 6;182(3):685-712.e19
pubmed: 32645325
RNA. 2013 Dec;19(12):1802-14
pubmed: 24149844
EMBO J. 1998 Oct 1;17(19):5783-95
pubmed: 9755178
J Cell Biol. 1994 Dec;127(6 Pt 1):1505-14
pubmed: 7798307
Nat Rev Mol Cell Biol. 2021 Mar;22(3):165-182
pubmed: 32873929
Front Genet. 2021 Mar 02;12:652129
pubmed: 33737950
Biochemistry. 1993 Sep 21;32(37):9754-62
pubmed: 8373778
RNA Biol. 2017 Jun 3;14(6):693-700
pubmed: 27775477
Wiley Interdiscip Rev RNA. 2013 Jan-Feb;4(1):17-34
pubmed: 23042601
Cell. 2015 Dec 3;163(6):1515-26
pubmed: 26627737
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Mol Biol Cell. 2002 Jan;13(1):362-81
pubmed: 11809845
Nature. 2020 Jul;583(7815):310-313
pubmed: 32494006
EMBO J. 2002 Jun 3;21(11):2746-56
pubmed: 12032087
Nucleic Acids Res. 2016 Sep 19;44(16):7884-95
pubmed: 27257078
Front Oncol. 2020 Jun 18;10:893
pubmed: 32626654
Curr Opin Cell Biol. 2015 Jun;34:23-30
pubmed: 25942753
Sci Rep. 2017 Sep 13;7(1):11490
pubmed: 28904332
Nucleic Acids Res. 2017 Feb 17;45(3):1433-1441
pubmed: 28180324
RNA. 2019 Jan;25(1):17-22
pubmed: 30301832
Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4334-9
pubmed: 21368180
Annu Rev Cell Biol. 1993;9:265-315
pubmed: 8280462
Mol Cell Biol. 2002 Dec;22(24):8457-66
pubmed: 12446766
Front Pharmacol. 2015 Mar 31;6:70
pubmed: 25873900
Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):E5593-601
pubmed: 25480548