Increased transcriptional elongation and RNA stability of GPCR ligand binding genes unveiled via RNA polymerase II degradation.

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  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
    • Publication Information:
      Publication: 1992- : Oxford : Oxford University Press
      Original Publication: London, Information Retrieval ltd.
    • Subject Terms:
      RNA Polymerase II*/metabolism ; RNA Polymerase II*/genetics ; RNA Stability* ; Transcription Elongation, Genetic*; Humans ; Ligands ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Jumonji Domain-Containing Histone Demethylases/genetics ; Alpha-Amanitin/pharmacology ; Phosphorylation ; RNA, Messenger/metabolism ; RNA, Messenger/genetics ; Histones/metabolism ; Proteolysis
    • Abstract:
      RNA polymerase II drives mRNA gene expression, yet our understanding of Pol II degradation is limited. Using auxin-inducible degron, we degraded Pol II's RPB1 subunit, resulting in global repression. Surprisingly, certain genes exhibited increased RNA levels post-degradation. These genes are associated with GPCR ligand binding and are characterized by being less paused and comprising polycomb-bound short genes. RPB1 degradation globally increased KDM6B binding, which was insufficient to explain specific gene activation. In contrast, RPB2 degradation repressed nearly all genes, accompanied by decreased H3K9me3 and SUV39H1 occupancy. We observed a specific increase in serine 2 phosphorylated Pol II and RNA stability for RPB1 degradation-upregulated genes. Additionally, α-amanitin or UV treatment resulted in RPB1 degradation and global gene repression, unveiling subsets of upregulated genes. Our findings highlight the activated transcription elongation and increased RNA stability of signaling genes as potential mechanisms for mammalian cells to counter RPB1 degradation during stress.
      (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
    • References:
      Cell. 2020 Mar 19;180(6):1228-1244.e24. (PMID: 32142649)
      Genes Dev. 2005 Dec 15;19(24):3004-16. (PMID: 16357218)
      Cell. 2007 Nov 30;131(5):901-14. (PMID: 18001825)
      FASEB J. 2002 Oct;16(12):1639-41. (PMID: 12207009)
      Genomics Proteomics Bioinformatics. 2021 Aug;19(4):578-583. (PMID: 34400360)
      Nat Rev Mol Cell Biol. 2021 Jan;22(1):3-21. (PMID: 33208928)
      Science. 2021 Jan 15;371(6526):305-309. (PMID: 33446560)
      Genome Biol. 2020 Jul 2;21(1):158. (PMID: 32616013)
      Genes Dev. 2020 Apr 1;34(7-8):465-488. (PMID: 32238450)
      Nucleic Acids Res. 2022 Jan 7;50(D1):D27-D38. (PMID: 34718731)
      Trends Cell Biol. 2021 May;31(5):359-371. (PMID: 33685798)
      Mol Cell. 2023 Apr 20;83(8):1280-1297.e11. (PMID: 36924766)
      Nucleic Acids Res. 2022 Jan 7;50(D1):D1522-D1527. (PMID: 34871441)
      Nat Immunol. 2022 May;23(5):671-678. (PMID: 35487986)
      Nucleic Acids Res. 2014 Dec 16;42(22):13674-88. (PMID: 25416796)
      Cell. 2020 Mar 19;180(6):1245-1261.e21. (PMID: 32142654)
      Cell Mol Life Sci. 2018 Oct;75(19):3473-3494. (PMID: 29779043)
      Trends Biochem Sci. 2012 Mar;37(3):99-105. (PMID: 22260999)
      Curr Opin Struct Biol. 2022 Aug;75:102404. (PMID: 35700575)
      Nature. 2023 Apr;616(7958):814-821. (PMID: 37046086)
      Nucleic Acids Res. 2019 Jan 8;47(D1):D1211-D1217. (PMID: 30252093)
      Cell. 2010 Nov 12;143(4):552-63. (PMID: 21074047)
      Biochim Biophys Acta Mol Cell Res. 2019 May;1866(5):773-792. (PMID: 30716408)
      Nat Genet. 2023 Feb;55(2):268-279. (PMID: 36658433)
      Methods. 2014 May 1;67(1):55-63. (PMID: 23872059)
      Genes Dev. 2015 Jan 1;29(1):39-47. (PMID: 25561494)
      Cell Mol Life Sci. 2019 Apr;76(8):1529-1539. (PMID: 30683982)
      Nucleic Acids Res. 1996 Aug 1;24(15):2924-9. (PMID: 8760875)
      Pharmacol Rev. 2012 Jul;64(3):645-75. (PMID: 22611178)
      Mol Cell. 2022 Oct 20;82(20):3943-3959.e11. (PMID: 36113479)
      Cell. 2013 May 9;153(4):855-68. (PMID: 23663783)
      FEBS Lett. 2015 Jun 22;589(14):1607-19. (PMID: 25980603)
      Science. 2005 Jul 15;309(5733):467-9. (PMID: 15947136)
      Nat Rev Microbiol. 2011 Feb;9(2):85-98. (PMID: 21233849)
      Nat Rev Mol Cell Biol. 2022 Sep;23(9):603-622. (PMID: 35505252)
      Leuk Lymphoma. 2015 May;56(5):1223-8. (PMID: 25115512)
      Mol Cell. 2020 May 21;78(4):765-778.e7. (PMID: 32298650)
      Transcription. 2023 Nov;14(1-2):49-67. (PMID: 37132022)
      Nature. 2015 Apr 30;520(7549):697-701. (PMID: 25901683)
      Curr Opin Clin Nutr Metab Care. 2007 Jul;10(4):397-402. (PMID: 17563455)
      Nature. 2017 Dec 14;552(7684):263-267. (PMID: 29186112)
      Genetics. 2014 Jul;197(3):839-49. (PMID: 24793090)
      Methods Mol Biol. 2018;1823:141-152. (PMID: 29959679)
      Nat Genet. 2021 May;53(5):719-728. (PMID: 33859416)
      Genome Biol. 2022 Nov 28;23(1):246. (PMID: 36443871)
      Prog Biophys Mol Biol. 2016 Jan;120(1-3):28-36. (PMID: 26772438)
      EMBO J. 2008 Dec 17;27(24):3256-66. (PMID: 19037258)
      Cell. 2012 Jul 20;150(2):279-90. (PMID: 22817891)
      Nat Genet. 2018 Jul;50(7):1002-1010. (PMID: 29808031)
      EMBO J. 2021 Aug 2;40(15):e105740. (PMID: 34254686)
      J Hepatol. 2007 Aug;47(2):262-9. (PMID: 17451837)
      Mol Cell. 2021 Jul 15;81(14):2944-2959.e10. (PMID: 34166609)
      Sci Adv. 2023 Apr 5;9(14):eade5397. (PMID: 37018397)
      Curr Opin Cell Biol. 2014 Apr;27:136-43. (PMID: 24534489)
      Mol Cell. 2022 Nov 17;82(22):4232-4245.e11. (PMID: 36309014)
      Cell. 2014 Feb 13;156(4):678-90. (PMID: 24529373)
      Nat Commun. 2019 Apr 3;10(1):1523. (PMID: 30944313)
      Cell Rep. 2020 Feb 11;30(6):1661-1669.e4. (PMID: 32049000)
      Mol Cell. 2024 Jan 4;84(1):70-79. (PMID: 38103560)
      Annu Rev Biochem. 2023 Jun 20;92:81-113. (PMID: 37040775)
      FASEB J. 2020 Oct;34(10):13900-13917. (PMID: 32830375)
      Nat Commun. 2022 Jun 24;13(1):3624. (PMID: 35750669)
      Nat Commun. 2022 Sep 28;13(1):5703. (PMID: 36171202)
      Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):E5593-601. (PMID: 25480548)
      Biochim Biophys Acta Gene Regul Mech. 2021 Feb;1864(2):194600. (PMID: 32645359)
      Cell Rep. 2012 Dec 27;2(6):1670-83. (PMID: 23260668)
      Methods. 2019 Apr 15;159-160:29-34. (PMID: 30797902)
      Proc Natl Acad Sci U S A. 2013 May 21;110(21):8531-6. (PMID: 23657011)
      Cell. 2017 Mar 23;169(1):13-23. (PMID: 28340338)
      Nat Cell Biol. 2007 Dec;9(12):1428-35. (PMID: 18037880)
      Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4239-44. (PMID: 11904382)
      Genome Biol. 2020 Feb 7;21(1):32. (PMID: 32033573)
      Nat Rev Mol Cell Biol. 2019 Dec;20(12):766-784. (PMID: 31558824)
      Biochim Biophys Acta Gene Regul Mech. 2021 Jan;1864(1):194659. (PMID: 33271312)
    • Grant Information:
      National Natural Science Foundation of China; 32350003 National Key R&D Program of China; 2017M610700 China Postdoctoral Science Foundation
    • Accession Number:
      EC 2.7.7.- (RNA Polymerase II)
      0 (Ligands)
      EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases)
      0 (Alpha-Amanitin)
      0 (RNA, Messenger)
      0 (Histones)
    • Publication Date:
      Date Created: 20240606 Date Completed: 20240811 Latest Revision: 20240813
    • Publication Date:
      20240813
    • Accession Number:
      PMC11317166
    • Accession Number:
      10.1093/nar/gkae478
    • Accession Number:
      38842922