دورية أكاديمية
أعرض في EDS

The spliceosome impacts morphogenesis in the human fungal pathogen Candida albicans .

التفاصيل البيبلوغرافية
العنوان: The spliceosome impacts morphogenesis in the human fungal pathogen Candida albicans .
المؤلفون: Lash E; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada., Maufrais C; Unité Biologie des ARN des Pathogènes Fongiques, Institut Pasteur, Université Paris Cité, Paris, France.; HUB Bioinformatique et Biostatistique, Institut Pasteur, Université Paris Cité, Paris, France., Janbon G; Unité Biologie des ARN des Pathogènes Fongiques, Institut Pasteur, Université Paris Cité, Paris, France., Robbins N; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada., Herzel L; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany., Cowen LE; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
المصدر: MBio [mBio] 2024 Aug 14; Vol. 15 (8), pp. e0153524. Date of Electronic Publication: 2024 Jul 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Society for Microbiology
مواضيع طبية MeSH: Candida albicans*/genetics , Candida albicans*/pathogenicity , Candida albicans*/growth & development , Candida albicans*/physiology , Candida albicans*/metabolism , Spliceosomes*/genetics , Spliceosomes*/metabolism , Gene Expression Regulation, Fungal* , Fungal Proteins*/genetics , Fungal Proteins*/metabolism, Humans ; Morphogenesis/genetics ; RNA Splicing ; Virulence ; Hyphae/growth & development ; Hyphae/genetics ; Introns/genetics
مستخلص: At human body temperature, the fungal pathogen Candida albicans can transition from yeast to filamentous morphologies in response to host-relevant cues. Additionally, elevated temperatures encountered during febrile episodes can independently induce C. albicans filamentation. However, the underlying genetic pathways governing this developmental transition in response to elevated temperatures remain largely unexplored. Here, we conducted a functional genomic screen to unravel the genetic mechanisms orchestrating C. albicans filamentation specifically in response to elevated temperature, implicating 45% of genes associated with the spliceosome or pre-mRNA splicing in this process. Employing RNA-Seq to elucidate the relationship between mRNA splicing and filamentation, we identified greater levels of intron retention in filaments compared to yeast, which correlated with reduced expression of the affected genes. Intriguingly, homozygous deletion of a gene encoding a spliceosome component important for filamentation ( PRP19 ) caused even greater levels of intron retention compared with wild type and displayed globally dysregulated gene expression. This suggests that intron retention is a mechanism for fine-tuning gene expression during filamentation, with perturbations of the spliceosome exacerbating this process and blocking filamentation. Overall, this study unveils a novel biological process governing C. albicans filamentation, providing new insights into the complex regulation of this key virulence trait.IMPORTANCEFungal pathogens such as Candida albicans can cause serious infections with high mortality rates in immunocompromised individuals. When C. albicans is grown at temperatures encountered during human febrile episodes, yeast cells undergo a transition to filamentous cells, and this process is key to its virulence. Here, we expanded our understanding of how C. albicans undergoes filamentation in response to elevated temperature and identified many genes involved in mRNA splicing that positively regulate filamentation. Through transcriptome analyses, we found that intron retention is a mechanism for fine-tuning gene expression in filaments, and perturbation of the spliceosome exacerbates intron retention and alters gene expression substantially, causing a block in filamentation. This work adds to the growing body of knowledge on the role of introns in fungi and provides new insights into the cellular processes that regulate a key virulence trait in C. albicans .
Competing Interests: L.E.C. is a co-founder and shareholder in Bright Angel Therapeutics, a platform company for the development of novel antifungal therapeutics. L.E.C. is a science advisor for Kapoose Creek, a company that harnesses the therapeutic potential of fungi. All other authors have no conflicts of interest to declare.
References: Nature. 2019 Jan;565(7741):612-617. (PMID: 30651641)
Mol Microbiol. 2003 Oct;50(1):167-81. (PMID: 14507372)
Mol Cell. 2003 Jul;12(1):5-14. (PMID: 12887888)
Genome Biol. 2008;9(3):R50. (PMID: 18321378)
Environ Microbiol. 2017 Oct;19(10):4065-4079. (PMID: 28654215)
Lancet Infect Dis. 2024 Jul;24(7):e428-e438. (PMID: 38224705)
PLoS Pathog. 2009 Feb;5(2):e1000294. (PMID: 19197361)
Microbiol Mol Biol Rev. 2011 Jun;75(2):213-67. (PMID: 21646428)
mSphere. 2020 Aug 12;5(4):. (PMID: 32817456)
Nature. 1999 Sep 9;401(6749):177-80. (PMID: 10490028)
Mol Cell. 2013 Aug 8;51(3):338-48. (PMID: 23891561)
Infect Immun. 2013 Apr;81(4):1267-76. (PMID: 23381995)
J Fungi (Basel). 2018 Mar 20;4(1):. (PMID: 30152809)
PLoS Genet. 2010 Aug 19;6(8):e1001070. (PMID: 20808890)
Curr Biol. 2009 Apr 28;19(8):621-9. (PMID: 19327993)
PLoS Genet. 2016 Nov 21;12(11):e1006452. (PMID: 27870871)
Nature. 2019 Jan;565(7741):606-611. (PMID: 30651636)
Fungal Biol. 2011 Jun;115(6):541-6. (PMID: 21640317)
Mol Microbiol. 2005 May;56(3):649-69. (PMID: 15819622)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Nature. 2022 May;605(7908):113-118. (PMID: 35444278)
Curr Genet. 2000 Feb;37(2):94-103. (PMID: 10743565)
Nat Commun. 2015 Mar 31;6:6741. (PMID: 25824284)
Sci Rep. 2016 Aug 31;6:32252. (PMID: 27577684)
Nat Rev Microbiol. 2017 Feb;15(2):96-108. (PMID: 27867199)
Curr Opin Microbiol. 2023 Oct;75:102351. (PMID: 37399670)
Genetics. 2022 Nov 30;222(4):. (PMID: 36226807)
PLoS Biol. 2011 Jul;9(7):e1001105. (PMID: 21811397)
DNA Res. 2014 Feb;21(1):27-39. (PMID: 24122896)
Genome Res. 2007 Apr;17(4):492-502. (PMID: 17351132)
Nat Commun. 2021 Nov 11;12(1):6497. (PMID: 34764269)
Antimicrob Agents Chemother. 2023 Jun 29;67(7):e0050323. (PMID: 37382550)
Nucleic Acids Res. 2017 Jan 4;45(D1):D592-D596. (PMID: 27738138)
Fungal Genet Biol. 2005 Oct;42(10):862-72. (PMID: 16098776)
Front Microbiol. 2018 Oct 02;9:2313. (PMID: 30333805)
Nucleic Acids Res. 2012 Jan;40(Database issue):D700-5. (PMID: 22110037)
PLoS Biol. 2007 Apr;5(4):e90. (PMID: 17388687)
FEMS Yeast Res. 2012 Feb;12(1):61-8. (PMID: 22094058)
mSphere. 2016 Jun 15;1(3):. (PMID: 27340698)
Trends Microbiol. 2017 Oct;25(10):809-819. (PMID: 28549824)
EMBO J. 2011 May 18;30(10):2008-18. (PMID: 21487390)
Sci Rep. 2017 Jul 18;7(1):5692. (PMID: 28720834)
Infect Immun. 2009 Sep;77(9):4150-60. (PMID: 19596778)
mBio. 2023 Apr 25;14(2):e0343422. (PMID: 36809010)
Genetics. 2021 Oct 2;219(2):. (PMID: 34143207)
Genetics. 2016 Nov;204(3):1239-1248. (PMID: 27630196)
Genome Biol. 2017 Mar 15;18(1):51. (PMID: 28298237)
Genes Dev. 1999 Dec 15;13(24):3271-9. (PMID: 10617575)
Nat Methods. 2015 Apr;12(4):357-60. (PMID: 25751142)
Nucleic Acids Res. 2017 Jul 7;45(12):7416-7431. (PMID: 28482101)
RNA. 1999 Sep;5(9):1138-9. (PMID: 10496214)
PLoS Genet. 2014 Apr 10;10(4):e1004249. (PMID: 24722551)
Bioinformatics. 2009 Aug 15;25(16):2078-9. (PMID: 19505943)
Genome Res. 2010 Oct;20(10):1451-8. (PMID: 20810668)
mBio. 2023 Dec 19;14(6):e0274523. (PMID: 38038475)
iScience. 2023 Feb 04;26(3):106145. (PMID: 36879823)
Nat Rev Microbiol. 2011 Aug 16;9(10):737-48. (PMID: 21844880)
Eukaryot Cell. 2007 Oct;6(10):1824-40. (PMID: 17715368)
Int Rev Cell Mol Biol. 2009;272:149-89. (PMID: 19121818)
PLoS Pathog. 2010 Nov 18;6(11):e1001193. (PMID: 21124988)
Bioinformatics. 2010 Mar 15;26(6):841-2. (PMID: 20110278)
Mol Cell. 2007 Sep 21;27(6):928-37. (PMID: 17889666)
Nat Genet. 2010 Jul;42(7):590-8. (PMID: 20543849)
Brief Bioinform. 2013 Mar;14(2):178-92. (PMID: 22517427)
G3 (Bethesda). 2017 Nov 6;7(11):3797-3808. (PMID: 28951491)
Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15974-9. (PMID: 15492211)
G3 (Bethesda). 2021 Feb 9;11(2):. (PMID: 33585865)
معلومات مُعتمدة: FDN-154288 Canadian Government | Canadian Institutes of Health Research (CIHR); R01AI127375 HHS | National Institutes of Health (NIH)
فهرسة مساهمة: Keywords: Candida albicans; filamentation; fungal pathogen; intron; morphogenesis; spliceosome; temperature
المشرفين على المادة: 0 (Fungal Proteins)
تواريخ الأحداث: Date Created: 20240709 Date Completed: 20240814 Latest Revision: 20240815
رمز التحديث: 20240815
DOI: 10.1128/mbio.01535-24
PMID: 38980041
قاعدة البيانات: MEDLINE
الوصف
تدمد:2150-7511
DOI:10.1128/mbio.01535-24