A prometastatic splicing program regulated by SNRPA1 interactions with structured RNA elements.
Adaptor Proteins, Signal Transducing
/ genetics
Algorithms
Alternative Splicing
Animals
Binding Sites
Breast Neoplasms
/ genetics
Cell Line, Tumor
Disease Progression
Exons
Gene Knockdown Techniques
Humans
Lung Neoplasms
/ secondary
Mice
Mice, Inbred NOD
Mice, SCID
Neoplasm Invasiveness
Neoplasm Metastasis
/ genetics
Neoplasm Transplantation
Nucleic Acid Conformation
Plectin
/ genetics
Protein Binding
RNA
/ genetics
RNA Interference
RNA, Small Nuclear
/ chemistry
RNA-Seq
Ribonucleoprotein, U2 Small Nuclear
/ genetics
Software
Spliceosomes
/ metabolism
Tumor Suppressor Proteins
/ genetics
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
14 05 2021
14 05 2021
Historique:
received:
13
05
2020
accepted:
01
04
2021
entrez:
14
5
2021
pubmed:
15
5
2021
medline:
26
5
2021
Statut:
ppublish
Résumé
Aberrant alternative splicing is a hallmark of cancer, yet the underlying regulatory programs that control this process remain largely unknown. Here, we report a systematic effort to decipher the RNA structural code that shapes pathological splicing during breast cancer metastasis. We discovered a previously unknown structural splicing enhancer that is enriched near cassette exons with increased inclusion in highly metastatic cells. We show that the spliceosomal protein small nuclear ribonucleoprotein polypeptide A' (SNRPA1) interacts with these enhancers to promote cassette exon inclusion. This interaction enhances metastatic lung colonization and cancer cell invasion, in part through SNRPA1-mediated regulation of
Identifiants
pubmed: 33986153
pii: 372/6543/eabc7531
doi: 10.1126/science.abc7531
pmc: PMC8238114
mid: NIHMS1715943
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
ERRFI1 protein, human
0
Plectin
0
RNA, Small Nuclear
0
Ribonucleoprotein, U2 Small Nuclear
0
Tumor Suppressor Proteins
0
U2 small nuclear RNA
0
U2A' protein, human
0
RNA
63231-63-0
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
Subventions
Organisme : Medical Research Council
ID : MR/P009417/1
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R00 CA194077
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA240984
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA108462
Pays : United States
Informations de copyright
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Références
Cell. 1985 Oct;42(3):737-50
pubmed: 2996775
Cell. 1993 Mar 26;72(6):881-92
pubmed: 8458082
J Cell Sci. 2011 Jun 1;124(Pt 11):1785-93
pubmed: 21576352
Nat Commun. 2020 Oct 9;11(1):5120
pubmed: 33037194
Genome Res. 2019 Jun;29(6):896-906
pubmed: 31152051
Nature. 2011 May 19;473(7347):337-42
pubmed: 21593866
Curr Opin Genet Dev. 2011 Aug;21(4):373-9
pubmed: 21530232
Mol Cell. 2014 Jun 5;54(5):887-900
pubmed: 24837674
Nature. 2014 Sep 11;513(7517):256-60
pubmed: 25043050
Nature. 2012 Apr 08;485(7397):264-8
pubmed: 22495308
Methods. 2020 Jun 1;178:72-82
pubmed: 31586594
Nat Genet. 2008 Dec;40(12):1413-5
pubmed: 18978789
BMC Bioinformatics. 2010 Mar 15;11:129
pubmed: 20230624
Algorithms Mol Biol. 2011 Nov 24;6:26
pubmed: 22115189
Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):10322-7
pubmed: 27578869
Mol Cell. 2019 Sep 5;75(5):967-981.e9
pubmed: 31300274
Nature. 2005 Jul 28;436(7050):518-24
pubmed: 16049480
Genome Res. 2018 Aug;28(8):1111-1125
pubmed: 30012835
RNA. 2018 Oct;24(10):1326-1338
pubmed: 30042172
Clin Exp Metastasis. 2018 Aug;35(5-6):393-402
pubmed: 29845349
Trends Pharmacol Sci. 2018 Nov;39(11):982-994
pubmed: 30282590
Proc Natl Acad Sci U S A. 2018 Apr 10;115(15):E3426-E3435
pubmed: 29581274
Biochemistry. 2014 Jun 17;53(23):3727-37
pubmed: 24866816
Nat Protoc. 2014 Feb;9(2):263-93
pubmed: 24407355
Genes Dev. 2014 Jun 1;28(11):1191-203
pubmed: 24840202
FEBS Lett. 2018 Sep;592(17):2987-3006
pubmed: 29856907
Mol Biol Cell. 2015 Jul 1;26(13):2402-17
pubmed: 25971800
Semin Cell Dev Biol. 2016 Feb;50:115-24
pubmed: 26456277
Eur J Cell Biol. 2014 Apr;93(4):157-69
pubmed: 24810881
Nat Methods. 2010 Dec;7(12):1009-15
pubmed: 21057496
Cold Spring Harb Perspect Biol. 2019 Nov 1;11(11):
pubmed: 30765414
Genes Dev. 1989 Oct;3(10):1553-61
pubmed: 2558966
PLoS One. 2010 Aug 06;5(8):e11981
pubmed: 20700505
Proc Natl Acad Sci U S A. 2009 Jun 30;106(26):10626-31
pubmed: 19541640
Oncogenesis. 2016 Dec 19;5(12):e280
pubmed: 27991914
Nature. 1998 Aug 13;394(6694):645-50
pubmed: 9716128
Nature. 2013 Oct 17;502(7471):385-8
pubmed: 24056935
Nature. 2008 Nov 27;456(7221):470-6
pubmed: 18978772
Nat Methods. 2016 Jun;13(6):489-92
pubmed: 27111506
Nature. 2020 Feb;578(7793):129-136
pubmed: 32025019
Mol Cell. 2015 Oct 1;60(1):105-17
pubmed: 26431027
Cell. 2006 Mar 24;124(6):1283-98
pubmed: 16564017
J Clin Invest. 2011 Mar;121(3):1064-74
pubmed: 21393860
Genome Res. 2015 Feb;25(2):290-303
pubmed: 25561518
Nature. 2015 Oct 1;526(7571):131-5
pubmed: 26416748
RNA. 2016 Sep;22(9):1285-301
pubmed: 27530828
Front Mol Biosci. 2018 Sep 07;5:80
pubmed: 30246013
Nat Methods. 2018 Mar;15(3):207-212
pubmed: 29400715
Annu Rev Biochem. 2015;84:291-323
pubmed: 25784052
Semin Cell Dev Biol. 2018 Mar;75:13-22
pubmed: 28919308
Nat Protoc. 2016 Dec;11(12):2301-2319
pubmed: 27809316
Cancer Res. 2013 Sep 1;73(17):5320-7
pubmed: 23867476
Nat Rev Cancer. 2019 Aug;19(8):465-478
pubmed: 31278396
Cell Rep. 2017 Aug 29;20(9):2215-2226
pubmed: 28854369
Wiley Interdiscip Rev RNA. 2018 Jul;9(4):e1476
pubmed: 29693319
Sci Rep. 2014 Nov 14;4:7063
pubmed: 25394353
Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):97-102
pubmed: 19109441
Dev Cell. 2020 Nov 9;55(3):298-313.e10
pubmed: 33171110
Curr Opin Genet Dev. 2018 Feb;48:16-21
pubmed: 29080552
Nat Struct Mol Biol. 2017 Oct 5;24(10):791-799
pubmed: 28981077
J Clin Invest. 2018 Apr 2;128(4):1371-1383
pubmed: 29480819
Nat Methods. 2016 Sep;13(9):731-40
pubmed: 27348712
J Clin Invest. 2005 Jan;115(1):44-55
pubmed: 15630443
Nat Methods. 2017 Jan;14(1):75-82
pubmed: 27819661
PLoS Genet. 2007 Nov;3(11):e204
pubmed: 18020710