Long non-coding RNA generated from CDKN1A gene by alternative polyadenylation regulates p21 expression during DNA damage response.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
27 Nov 2023
27 Nov 2023
Historique:
accepted:
12
10
2023
revised:
21
09
2023
received:
27
12
2022
medline:
29
11
2023
pubmed:
23
10
2023
entrez:
23
10
2023
Statut:
ppublish
Résumé
Alternative Polyadenylation (APA) is an emerging mechanism for dynamic changes in gene expression. Previously, we described widespread APA occurrence in introns during the DNA damage response (DDR). Here, we show that a DDR-activated APA event occurs in the first intron of CDKN1A, inducing an alternate last exon-containing lncRNA. We named this lncRNA SPUD (Selective Polyadenylation Upon DNA Damage). SPUD localizes to polysomes in the cytoplasm and is detectable as multiple isoforms in available high-throughput studies. SPUD has low abundance compared to the CDKN1A full-length isoform under non-stress conditions, and SPUD is induced in cancer and normal cells under a variety of DNA damaging conditions in part through p53. The RNA binding protein HuR binds to and promotes the stability of SPUD precursor RNA. SPUD induction increases p21 protein, but not mRNA levels, affecting p21 functions in cell-cycle, CDK2 expression and cell growth. Like CDKN1A full-length isoform, SPUD can bind two competitive p21 translational regulators, the inhibitor calreticulin and the activator CUGBP1; SPUD alters their association with CDKN1A full-length in a DDR-dependent manner, promoting CDKN1A translation. Together, these results show a new regulatory mechanism by which a lncRNA controls p21 expression post-transcriptionally, highlighting lncRNA relevance in DDR progression and cell-cycle.
Identifiants
pubmed: 37870464
pii: 7327065
doi: 10.1093/nar/gkad899
pmc: PMC10681730
doi:
Substances chimiques
CDKN1A protein, human
0
Cyclin-Dependent Kinase Inhibitor p21
0
Protein Isoforms
0
RNA, Long Noncoding
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
11911-11926Subventions
Organisme : NCI NIH HHS
ID : U54 CA221704
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA204610-01
Pays : United States
Organisme : NIH HHS
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
Sci Rep. 2020 Oct 1;10(1):16245
pubmed: 33004865
Cell. 2001 Mar 9;104(5):743-53
pubmed: 11257228
Oncogenesis. 2019 Dec 10;8(12):73
pubmed: 31822653
J Biol Chem. 2002 May 10;277(19):17154-60
pubmed: 11877436
Cancers (Basel). 2022 Jul 20;14(14):
pubmed: 35884580
Transcription. 2022 Aug-Oct;13(4-5):89-95
pubmed: 36004392
Mol Cell Biol. 2000 Feb;20(3):760-9
pubmed: 10629032
Nat Rev Cancer. 2009 Jun;9(6):400-14
pubmed: 19440234
Int J Mol Sci. 2020 Apr 23;21(8):
pubmed: 32340118
Nature. 2019 Aug;572(7769):321-322
pubmed: 31406309
Nature. 2018 Sep;561(7721):127-131
pubmed: 30150773
Mol Cell. 2011 Aug 5;43(3):327-39
pubmed: 21723170
EMBO J. 2010 May 19;29(10):1674-87
pubmed: 20379136
Genes Dev. 2009 Jun 1;23(11):1364-77
pubmed: 19487575
Genes Dev. 2011 Apr 1;25(7):701-16
pubmed: 21460037
Carcinogenesis. 2002 Aug;23(8):1289-96
pubmed: 12151346
Nucleic Acids Res. 2015 Dec 15;43(22):10925-38
pubmed: 26400160
Nat Genet. 2008 Dec;40(12):1413-5
pubmed: 18978789
EMBO J. 2004 Jan 28;23(2):406-17
pubmed: 14726956
DNA Repair (Amst). 2016 Jun;42:63-71
pubmed: 27156098
Mamm Genome. 2022 Jun;33(2):271-280
pubmed: 34406447
Nat Methods. 2013 Feb;10(2):133-9
pubmed: 23241633
Genes Dev. 2011 Sep 15;25(18):1915-27
pubmed: 21890647
Clin Chem. 2009 Apr;55(4):611-22
pubmed: 19246619
Nature. 1996 Jun 20;381(6584):713-6
pubmed: 8649519
Cell Signal. 2010 Jul;22(7):1003-12
pubmed: 20100570
PLoS Genet. 2021 Jul 28;17(7):e1009683
pubmed: 34319983
Algorithms Mol Biol. 2011 Nov 24;6:26
pubmed: 22115189
Science. 2011 Jan 7;331(6013):76-9
pubmed: 21127216
J Biol Chem. 2021 Jan-Jun;296:100036
pubmed: 33410401
Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14937-42
pubmed: 10611316
Methods Mol Biol. 2022;2404:53-65
pubmed: 34694603
Mol Cell Biol. 2007 Feb;27(4):1309-20
pubmed: 17158927
Genes Dev. 1991 Nov;5(11):2086-95
pubmed: 1657710
Nat Rev Mol Cell Biol. 2017 Jan;18(1):18-30
pubmed: 27677860
J Biol Chem. 2002 Oct 25;277(43):40513-9
pubmed: 12183457
Nucleic Acids Res. 2015 Jan;43(Database issue):D670-81
pubmed: 25428374
Cancer Res. 1995 Nov 15;55(22):5187-90
pubmed: 7585571
Cell Rep. 2019 Mar 5;26(10):2766-2778.e6
pubmed: 30840896
PLoS One. 2011;6(5):e20254
pubmed: 21637851
Cell. 2019 Jul 11;178(2):361-373.e12
pubmed: 31204100
Bioinformatics. 2011 Jul 1;27(13):i275-82
pubmed: 21685081
Genome Res. 2007 Feb;17(2):156-65
pubmed: 17210931
Int J Oncol. 2020 Jun;56(6):1574-1584
pubmed: 32236605
Nature. 2018 Dec;564(7734):141-145
pubmed: 30487607
Cell Discov. 2016 Jun 14;2:16013
pubmed: 27462460
Aging Cell. 2017 Oct;16(5):1094-1103
pubmed: 28691365
Nucleic Acids Res. 2016 Mar 18;44(5):2378-92
pubmed: 26819413
J Biol Chem. 2008 Oct 24;283(43):29045-52
pubmed: 18703516
Elife. 2014 Sep 16;3:e03523
pubmed: 25233276
Nucleic Acids Res. 1999 Nov 15;27(22):4517-25
pubmed: 10536163
Nucleic Acids Res. 2003 Jan 1;31(1):51-4
pubmed: 12519945
Nat Commun. 2014 Feb 28;5:3395
pubmed: 24577238
Nat Commun. 2021 Jul 1;12(1):4075
pubmed: 34210972
J Cell Sci. 2016 Nov 1;129(21):4025-4033
pubmed: 27609837
Cell. 2003 Sep 5;114(5):599-610
pubmed: 13678583
Nat Cell Biol. 2017 Dec;19(12):1400-1411
pubmed: 29180822
Genome Res. 2022 Jul 20;:
pubmed: 35858751
Mol Cell Biol. 2015 May;35(9):1633-47
pubmed: 25733682
RNA Biol. 2018 Feb 1;15(2):251-260
pubmed: 29168431
Cell. 2017 Feb 23;168(5):843-855.e13
pubmed: 28215706
Nat Genet. 2011 Jun 05;43(7):621-9
pubmed: 21642992
Nat Genet. 2016 Nov;48(11):1370-1376
pubmed: 27668660
Nucleic Acids Res. 2010 Apr;38(7):2256-67
pubmed: 20064878
Nature. 2010 Dec 2;468(7324):664-8
pubmed: 20881964
Nucleic Acids Res. 2005 Jan 12;33(1):201-12
pubmed: 15647503
Cell Cycle. 2013 Jul 1;12(13):2051-60
pubmed: 23759594
Oncotarget. 2016 Feb 9;7(6):7120-33
pubmed: 26760768
Mol Cell. 2014 Jun 5;54(5):777-90
pubmed: 24857549
Mol Cell Biol. 2009 Jan;29(1):172-86
pubmed: 18955504
Genes Dev. 2006 Mar 1;20(5):601-12
pubmed: 16510875
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W361-7
pubmed: 24829458
Cell. 1993 Nov 19;75(4):817-25
pubmed: 8242752
Nucleic Acids Res. 2019 Jan 8;47(D1):D766-D773
pubmed: 30357393
Nature. 2013 Jul 18;499(7458):360-3
pubmed: 23792564
Mol Cell Biol. 1983 Dec;3(12):2151-5
pubmed: 6197625
Genome Res. 2018 Oct;28(10):1427-1441
pubmed: 30143597
Genome Res. 2019 Dec;29(12):2073-2087
pubmed: 31537640
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
RNA Biol. 2017 Mar 4;14(3):361-369
pubmed: 28080204
Mol Cell. 2003 Oct;12(4):1015-27
pubmed: 14580351
Cell. 2012 Jul 6;150(1):53-64
pubmed: 22770214
Mol Cell Biol. 2013 Apr;33(8):1582-93
pubmed: 23401853
RNA. 2016 Jun;22(6):867-82
pubmed: 27090285
Mol Biol Cell. 2018 Jan 1;29(1):29-41
pubmed: 29118075
Biochem Biophys Res Commun. 2012 Aug 3;424(3):469-75
pubmed: 22771799
Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3386-91
pubmed: 18287003
Genome Res. 2012 Jun;22(6):1173-83
pubmed: 22454233
Cell Rep. 2019 Jun 25;27(13):3808-3817.e7
pubmed: 31242415
Nat Commun. 2014 Nov 19;5:5323
pubmed: 25406515
Nat Rev Mol Cell Biol. 2021 Feb;22(2):96-118
pubmed: 33353982
Mol Cell. 2012 Aug 24;47(4):648-55
pubmed: 22841487
Mol Cell. 2011 Sep 16;43(6):853-66
pubmed: 21925375
J Cell Biochem. 2007 Apr 1;100(5):1276-87
pubmed: 17063487
Nat Rev Mol Cell Biol. 2022 Dec;23(12):779-796
pubmed: 35798852
PLoS One. 2012;7(5):e37759
pubmed: 22662213