A type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparum.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
22 06 2023
22 06 2023
Historique:
received:
19
10
2022
accepted:
12
06
2023
medline:
26
6
2023
pubmed:
23
6
2023
entrez:
22
6
2023
Statut:
epublish
Résumé
Protein arginine methyltransferases (PRMTs) regulate many important cellular processes, such as transcription and RNA processing in model organisms but their functions in human malaria parasites are not elucidated. Here, we characterize PfPRMT5 in Plasmodium falciparum, which catalyzes symmetric dimethylation of histone H3 at R2 (H3R2me2s) and R8, and histone H4 at R3 in vitro. PfPRMT5 disruption results in asexual stage growth defects primarily due to lower invasion efficiency of the merozoites. Transcriptomic analysis reveals down-regulation of many transcripts related to invasion upon PfPRMT5 disruption, in agreement with H3R2me2s being an active chromatin mark. Genome-wide chromatin profiling detects extensive H3R2me2s marking of genes of different cellular processes, including invasion-related genes in wildtype parasites and PfPRMT5 disruption leads to the depletion of H3R2me2s. Interactome studies identify the association of PfPRMT5 with invasion-related transcriptional regulators such as AP2-I, BDP1, and GCN5. Furthermore, PfPRMT5 is associated with the RNA splicing machinery, and PfPRMT5 disruption caused substantial anomalies in RNA splicing events, including those for invasion-related genes. In summary, PfPRMT5 is critical for regulating parasite invasion and RNA splicing in this early-branching eukaryote.
Identifiants
pubmed: 37349497
doi: 10.1038/s42003-023-05038-z
pii: 10.1038/s42003-023-05038-z
pmc: PMC10287762
doi:
Substances chimiques
Protein-Arginine N-Methyltransferases
EC 2.1.1.319
Histones
0
Chromatin
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
Pagination
659Subventions
Organisme : NIAID NIH HHS
ID : R01 AI128940
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI149202
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI089672
Pays : United States
Informations de copyright
© 2023. The Author(s).
Références
Genome Biol. 2012 Nov 26;13(11):R108
pubmed: 23181666
Cell Rep. 2012 Feb 23;1(2):83-90
pubmed: 22720264
Arch Biochem Biophys. 2016 Jan 15;590:138-152
pubmed: 26612103
Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20538-43
pubmed: 22143770
PLoS Pathog. 2021 Aug 17;17(8):e1009351
pubmed: 34403450
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
J Med Chem. 2018 Nov 8;61(21):9429-9441
pubmed: 29870258
Cell Mol Life Sci. 2017 Sep;74(18):3305-3315
pubmed: 28364192
Malar J. 2013 Sep 18;12:333
pubmed: 24047207
mBio. 2016 Feb 02;7(1):e02094-15
pubmed: 26838719
Int J Parasitol. 2010 Jan;40(1):109-21
pubmed: 19765590
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Nat Struct Mol Biol. 2019 Nov;26(11):999-1012
pubmed: 31611688
Cell Host Microbe. 2015 Jun 10;17(6):741-51
pubmed: 26067602
Cell Rep. 2016 Mar 15;14(10):2463-75
pubmed: 26947071
FEBS Lett. 2013 Apr 17;587(8):1247-57
pubmed: 23402885
FEBS Lett. 2011 Jul 7;585(13):2024-31
pubmed: 21074527
Nucleic Acids Res. 2014 Jan;42(1):235-48
pubmed: 24097435
Eukaryot Cell. 2004 Apr;3(2):264-76
pubmed: 15075257
Mol Cell Biol. 2004 Nov;24(21):9630-45
pubmed: 15485929
J Biol Chem. 2013 Jan 18;288(3):1590-602
pubmed: 23204525
Epigenetics Chromatin. 2019 Jul 12;12(1):42
pubmed: 31300027
Clin Cancer Res. 2019 Apr 15;25(8):2633-2643
pubmed: 30635341
Cell Host Microbe. 2017 Jun 14;21(6):731-741.e10
pubmed: 28618269
Science. 2003 Sep 12;301(5639):1503-8
pubmed: 12893887
EMBO J. 2015 Mar 12;34(6):748-58
pubmed: 25519955
Bioinformatics. 2011 Sep 1;27(17):2325-9
pubmed: 21697122
PLoS One. 2014 Feb 03;9(2):e87267
pubmed: 24498306
Genome Biol. 2014;15(12):550
pubmed: 25516281
Mol Cell. 2017 Oct 5;68(1):130-143.e5
pubmed: 28918903
Mol Microbiol. 2010 Apr;76(1):12-24
pubmed: 20141604
Mol Cell. 2017 Jan 5;65(1):8-24
pubmed: 28061334
J Cell Biochem. 2011 May;112(5):1295-310
pubmed: 21312235
Trends Genet. 2021 Jan;37(1):73-85
pubmed: 32988634
J Biol Chem. 2012 Nov 23;287(48):40641-51
pubmed: 23048028
Mol Cell. 2009 Jan 16;33(1):1-13
pubmed: 19150423
Nature. 2002 Oct 3;419(6906):537-42
pubmed: 12368870
Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10931-6
pubmed: 9380737
Nat Methods. 2015 Jan;12(1):7-8
pubmed: 25549265
Mol Cell Proteomics. 2022 Mar;21(3):100199
pubmed: 35051657
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7289-94
pubmed: 8692985
Pharmacol Ther. 2007 Jan;113(1):50-87
pubmed: 17005254
Nat Struct Mol Biol. 2012 Jan 08;19(2):136-44
pubmed: 22231400
Cell Host Microbe. 2017 Aug 9;22(2):232-245
pubmed: 28799908
J Proteomics. 2014 Apr 04;100:37-43
pubmed: 24513533
Eukaryot Cell. 2007 Apr;6(4):584-91
pubmed: 17307963
J Biol Chem. 2019 May 10;294(19):7692-7710
pubmed: 30885941
BMC Genomics. 2020 Jun 8;21(1):395
pubmed: 32513207
J Biol Chem. 2017 Feb 10;292(6):2089-2100
pubmed: 27998975
Nucleic Acids Res. 2015 May 19;43(9):4661-75
pubmed: 25870410
Nucleic Acids Res. 2012 Apr;40(8):e61
pubmed: 22266656
Nucleic Acids Res. 2009 Jan;37(Database issue):D539-43
pubmed: 18957442
Nat Commun. 2015 Jul 07;6:7285
pubmed: 26149123
J Proteome Res. 2022 Aug 5;21(8):1857-1867
pubmed: 35772009
Nucleic Acids Res. 2013 Jan;41(Database issue):D991-5
pubmed: 23193258
Mol Microbiol. 2010 Nov;78(4):883-902
pubmed: 20807207
Annu Rev Microbiol. 2018 Sep 08;72:355-375
pubmed: 29927705
Cell Death Differ. 2021 Sep;28(9):2818-2836
pubmed: 33953349
BMC Genomics. 2011 Nov 30;12:587
pubmed: 22129310
Int J Parasitol. 2008 Aug;38(10):1083-97
pubmed: 18299133
Genes Dev. 2010 Dec 15;24(24):2772-7
pubmed: 21159818
Genome Biol. 2010;11(10):R106
pubmed: 20979621
Wiley Interdiscip Rev Syst Biol Med. 2012 Nov-Dec;4(6):565-83
pubmed: 22899623
Parasit Vectors. 2015 Apr 10;8:219
pubmed: 25889855
Genome Biol. 2019 Aug 1;20(1):151
pubmed: 31370870
Eukaryot Cell. 2007 Sep;6(9):1665-81
pubmed: 17601874
Mol Cell. 2012 Jan 27;45(2):185-95
pubmed: 22169276
Biochem J. 2009 Jun 12;421(1):107-18
pubmed: 19344311
Oncotarget. 2018 Nov 30;9(94):36705-36718
pubmed: 30613353
Nat Protoc. 2011 Feb;6(2):140-6
pubmed: 21293455
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Science. 1981 May 29;212(4498):1037-8
pubmed: 7015505
PLoS Pathog. 2013;9(4):e1003268
pubmed: 23637595
Sci Signal. 2019 Apr 02;12(575):
pubmed: 30940768
Nat Protoc. 2019 Mar;14(3):703-721
pubmed: 30804569
Microb Genom. 2020 Feb;6(2):
pubmed: 32017676
Stem Cell Rev Rep. 2014 Apr;10(2):230-9
pubmed: 24477620
Mol Biochem Parasitol. 2004 Sep;137(1):13-21
pubmed: 15279947
J Biol Chem. 2001 Apr 6;276(14):11393-401
pubmed: 11152681
Mol Cell Biol. 2005 Dec;25(23):10301-14
pubmed: 16287846
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
J Clin Invest. 2015 Sep;125(9):3532-44
pubmed: 26258414
Curr Protoc Bioinformatics. 2014 Sep 08;47:11.12.1-34
pubmed: 25199790
Gene. 2020 Jun 5;742:144593
pubmed: 32199949
PLoS Biol. 2003 Oct;1(1):E5
pubmed: 12929205
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
pubmed: 11309499
Genome Res. 2012 Oct;22(10):2008-17
pubmed: 22722343
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
J Biol Chem. 2000 Jun 2;275(22):17122-9
pubmed: 10747894
Nucleic Acids Res. 2001 Feb 1;29(3):850-3
pubmed: 11160909
Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14378-83
pubmed: 20660744
J Proteome Res. 2016 Aug 5;15(8):2787-801
pubmed: 27291344
Nat Commun. 2019 Apr 29;10(1):1930
pubmed: 31036827
Nat Rev Cancer. 2013 Jan;13(1):37-50
pubmed: 23235912
Nucleic Acids Res. 2020 Apr 6;48(6):2956-2968
pubmed: 32025719
Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):17960-5
pubmed: 23071334
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552
pubmed: 34723319
Sci Rep. 2017 Apr 4;7(1):607
pubmed: 28377601
PLoS Pathog. 2010 Dec 16;6(12):e1001223
pubmed: 21187892
Cell Host Microbe. 2009 Feb 19;5(2):179-90
pubmed: 19218088
Gene. 2006 Mar 15;369:53-65
pubmed: 16410041
Microbiologyopen. 2014 Oct;3(5):595-609
pubmed: 25044453
Genes Dev. 2013 Sep 1;27(17):1903-16
pubmed: 24013503
Eukaryot Cell. 2005 Nov;4(11):1942-50
pubmed: 16278461
Nature. 2010 Nov 4;468(7320):112-6
pubmed: 20962777
Eukaryot Cell. 2011 Aug;10(8):1013-22
pubmed: 21685318
Science. 1976 Aug 20;193(4254):673-5
pubmed: 781840
Cell Cycle. 2014;13(1):32-41
pubmed: 24296620
Nucleic Acids Res. 2006 Feb 21;34(4):1166-73
pubmed: 16493140
J Biol Chem. 2002 Mar 8;277(10):8243-7
pubmed: 11756452
J Proteome Res. 2009 Jul;8(7):3439-50
pubmed: 19351122