Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

The conserved noncoding RNA ModT coordinates growth and virulence in Clostridioides difficile.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read Online Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science, [2003]-
    • Subject Terms:
      Clostridioides difficile*/genetics ; Clostridioides difficile*/pathogenicity ; Clostridioides difficile*/metabolism ; Gene Expression Regulation, Bacterial* ; RNA, Bacterial*/genetics ; RNA, Bacterial*/metabolism; Virulence/genetics ; Spores, Bacterial/genetics ; RNA, Untranslated/genetics ; RNA, Untranslated/metabolism ; Animals ; Cyclic GMP/metabolism ; Cyclic GMP/analogs & derivatives ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Mice ; Conserved Sequence
    • Abstract:
      Competing Interests: The authors have declared that no competing interests exist.
      Bacterial noncoding RNAs fulfill a variety of cellular functions as catalysts, as scaffolds in protein complexes or as regulators of gene expression. They often exhibit complex tertiary structures that are a key determinant of their biochemical function. Here, we characterize the structured "raiA motif" RNA from Clostridioides difficile, which is conserved in more than 2,500 bacterial species from the phyla Bacillota and Actinomycetota. We show that its transcript abundance and stability in exponentially growing bacteria rivals that of ribosomal RNAs. Deletion of the "raiA motif" RNA is associated with delayed transition into stationary phase, and changes in stationary phase pathways such as spore formation, hence we rename it ModT (modulator of transition phase). Mechanistically, we show that ModT-mediated changes in cellular cyclic di-GMP levels are linked to the pronounced sporulation defect in the modT mutant. Importantly, we show that expression profiles and isoform patterns of ModT are conserved in Clostridium perfringens and Paeniclostridium sordellii, and that these orthologs can functionally complement ModT in C. difficile. Chemical structure probing of ModT in vivo reveals dynamic refolding and provides initial evidence for a potential association of ModT with proteins. In summary, our findings indicate that ModT fulfills a conserved role in regulating growth transitions in bacteria and provide a crucial step towards delineating its molecular mechanism.
      (Copyright: © 2024 Lenče et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
    • References:
      Sci Signal. 2017 Jun 13;10(483):. (PMID: 28611182)
      Microbiol Spectr. 2018 Jul;6(4):. (PMID: 30003867)
      J Bacteriol. 2015 Mar;197(5):819-32. (PMID: 25512308)
      mSphere. 2021 Dec 22;6(6):e0091921. (PMID: 34878288)
      Environ Microbiol. 2017 May;19(5):1933-1958. (PMID: 28198085)
      Nat Rev Mol Cell Biol. 2024 Oct;25(10):784-801. (PMID: 38926530)
      Nat Methods. 2012 Jul;9(7):671-5. (PMID: 22930834)
      Curr Protoc Bioinformatics. 2018 Jun;62(1):e51. (PMID: 29927072)
      mSphere. 2020 Sep 16;5(5):. (PMID: 32938698)
      Microbiol Mol Biol Rev. 2021 Aug 18;85(3):e0006421. (PMID: 34076506)
      Nature. 2018 Jan 18;553(7688):291-294. (PMID: 29310122)
      PLoS Pathog. 2022 Jul 5;18(7):e1010677. (PMID: 35789350)
      Cell. 1983 Dec;35(3 Pt 2):849-57. (PMID: 6197186)
      PLoS Pathog. 2018 Mar 12;14(3):e1006940. (PMID: 29529083)
      Nature. 1982 Oct 21;299(5885):691-8. (PMID: 6181418)
      J Mol Biol. 2019 Jan 4;431(1):3-20. (PMID: 30193985)
      RNA. 2007 Jun;13(6):824-34. (PMID: 17438124)
      J Bacteriol. 2013 Nov;195(22):5174-85. (PMID: 24039264)
      EMBO J. 2003 Jul 15;22(14):3479-85. (PMID: 12853463)
      ACS Infect Dis. 2021 May 14;7(5):1126-1142. (PMID: 33176423)
      Nat Rev Genet. 2007 Oct;8(10):776-90. (PMID: 17846637)
      Nat Methods. 2023 Jun;20(6):849-859. (PMID: 37106231)
      Microlife. 2021 Apr 22;2:uqab004. (PMID: 37223250)
      Methods Mol Biol. 2021;2254:219-238. (PMID: 33326078)
      Nucleic Acids Res. 2021 Jan 8;49(D1):D192-D200. (PMID: 33211869)
      Science. 2010 Aug 13;329(5993):845-848. (PMID: 20705859)
      Nature. 2004 Mar 18;428(6980):281-6. (PMID: 15029187)
      J Bacteriol. 2011 Jul;193(13):3186-96. (PMID: 21572003)
      Nucleic Acids Res. 2018 Sep 19;46(16):e97. (PMID: 29893890)
      J Bacteriol. 2015 Nov 23;198(3):565-77. (PMID: 26598364)
      Microbiol Mol Biol Rev. 2023 Jun 28;87(2):e0008022. (PMID: 36927044)
      Nature. 2009 Dec 3;462(7273):656-9. (PMID: 19956260)
      Mol Microbiol. 2015 Jan;95(2):189-208. (PMID: 25393584)
      Trends Microbiol. 2022 Oct;30(10):959-972. (PMID: 35379550)
      Appl Environ Microbiol. 2012 Jul;78(13):4683-90. (PMID: 22522680)
      Infect Immun. 2012 Aug;80(8):2704-11. (PMID: 22615253)
      Proc Natl Acad Sci U S A. 2021 Jun 22;118(25):. (PMID: 34131082)
      EcoSal Plus. 2020 Mar;9(1):. (PMID: 32213244)
      Microbiol Spectr. 2019 Nov;7(6):. (PMID: 31858953)
      Nucleic Acids Res. 2017 Oct 13;45(18):10811-10823. (PMID: 28977401)
      Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):E6319-E6328. (PMID: 29915070)
      RNA. 2018 Feb;24(2):183-195. (PMID: 29109157)
      Bioinformatics. 2010 Jan 1;26(1):139-40. (PMID: 19910308)
      mSphere. 2018 Oct 24;3(5):. (PMID: 30355665)
      Proc Natl Acad Sci U S A. 1980 Dec;77(12):7112-6. (PMID: 6938958)
      Nat Methods. 2012 Mar 04;9(4):357-9. (PMID: 22388286)
      Nat Rev Microbiol. 2017 May;15(5):271-284. (PMID: 28163311)
      Microbiol Spectr. 2014 Oct;2(5):. (PMID: 26104355)
      Biochem Soc Trans. 2019 Apr 30;47(2):527-539. (PMID: 30837318)
      EMBO J. 2023 Jun 15;42(12):e112858. (PMID: 37140366)
      Nat Commun. 2014;5:3114. (PMID: 24445449)
      Mol Microbiol. 2023 Sep;120(3):324-340. (PMID: 37469248)
      Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19490-5. (PMID: 17164334)
      Bioinformatics. 2014 Dec 1;30(23):3421-3. (PMID: 25123900)
      PLoS Genet. 2013;9(8):e1003660. (PMID: 23950727)
      Methods. 2001 Dec;25(4):402-8. (PMID: 11846609)
      PLoS Genet. 2011 Mar;7(3):e1002039. (PMID: 21483756)
      Proc Natl Acad Sci U S A. 2024 Feb 6;121(6):e2318008121. (PMID: 38306478)
      mBio. 2023 Feb 28;14(1):e0280522. (PMID: 36598190)
      Cell. 2014 Mar 27;157(1):77-94. (PMID: 24679528)
      Nucleic Acids Res. 2012 Aug;40(14):6898-907. (PMID: 22561371)
      J Bacteriol. 2012 Jul;194(13):3307-16. (PMID: 22522894)
      Nucleic Acids Res. 2018 Jul 27;46(13):6797-6805. (PMID: 29669055)
      Nat Struct Biol. 2000 Jun;7(6):449-55. (PMID: 10881189)
      Infect Immun. 2014 Oct;82(10):4276-91. (PMID: 25069979)
    • Accession Number:
      0 (RNA, Bacterial)
      0 (RNA, Untranslated)
      61093-23-0 (bis(3',5')-cyclic diguanylic acid)
      H2D2X058MU (Cyclic GMP)
      0 (Bacterial Proteins)
    • Publication Date:
      Date Created: 20241213 Date Completed: 20250108 Latest Revision: 20250109
    • Publication Date:
      20250110
    • Accession Number:
      PMC11706538
    • Accession Number:
      10.1371/journal.pbio.3002948
    • Accession Number:
      39671441