Expression of TNRC6 (GW182) Proteins Is Not Necessary for Gene Silencing by Fully Complementary RNA Duplexes.

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  • Author(s): Liu Z;Liu Z;Liu Z; Johnson ST; Johnson ST; Zhang Z; Zhang Z; Corey DR; Corey DR
  • Source:
    Nucleic acid therapeutics [Nucleic Acid Ther] 2019 Dec; Vol. 29 (6), pp. 323-334. Date of Electronic Publication: 2019 Oct 31.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 101562758 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2159-3345 (Electronic) Linking ISSN: 21593337 NLM ISO Abbreviation: Nucleic Acid Ther Subsets: MEDLINE
    • Publication Information:
      Original Publication: New Rochelle, N.Y. : Mary Ann Liebert, Inc.
    • Subject Terms:
      Argonaute Proteins/*genetics ; Autoantigens/*genetics ; Genetic Therapy/*methods ; RNA-Binding Proteins/*genetics; Argonaute Proteins/antagonists & inhibitors ; Argonaute Proteins/therapeutic use ; Autoantigens/therapeutic use ; Cytoplasm/genetics ; Gene Expression Regulation/genetics ; Gene Silencing ; Humans ; MicroRNAs/genetics ; Promoter Regions, Genetic/genetics ; RNA-Binding Proteins/antagonists & inhibitors ; RNA-Binding Proteins/therapeutic use ; Trinucleotide Repeats/genetics
    • Abstract:
      The trinucleotide repeat containing 6 (TNRC6) family of proteins are core components of RNA interference (RNAi) and consist of three paralogs (TNRC6A, TNRC6B, and TNRC6C). The TNRC6 paralogs associate with argonaute (AGO) protein, the core RNAi factor, and bridge its interactions with other proteins. We obtained TNRC6A and TNRC6B single and double knockout cell lines to investigate how the TNRC6 paralogs contribute to RNAi. We found that TNRC6 proteins are not required for gene silencing when duplex RNAs are fully complementary. TNRC6 expression was necessary for regulation by a microRNA. TNRC6A, but not TNRC6B, expression was necessary for transcriptional activation by a duplex RNA targeting a gene promoter. By contrast, AGO2 is required for all three gene expression pathways. TNRC6A can affect the Dicer localization in cytoplasm versus the nucleus, but none of the three TNRC6 paralogs was necessary for nuclear localization of AGO2. Our data suggest that the roles of the TNRC6 paralogs differ in some details and that TNRC6 is not required for clinical therapeutic silencing mechanisms that involve fully complementary duplex RNAs.
    • References:
      RNA. 2016 Jul;22(7):1085-98. (PMID: 27198507)
      Oncotarget. 2016 Jun 7;7(23):34288-99. (PMID: 27144431)
      Cell Rep. 2014 Jan 16;6(1):211-21. (PMID: 24388755)
      Cell. 2015 Oct 22;163(3):712-23. (PMID: 26496610)
      Mol Biol Cell. 2002 Apr;13(4):1338-51. (PMID: 11950943)
      Cell Rep. 2017 Aug 15;20(7):1543-1552. (PMID: 28813667)
      Biochemistry. 2018 Sep 4;57(35):5247-5256. (PMID: 30086238)
      Genes Dev. 2012 Apr 1;26(7):693-704. (PMID: 22474261)
      PLoS One. 2017 Aug 24;12(8):e0183587. (PMID: 28837617)
      Int J Biochem Cell Biol. 2018 Aug;101:29-38. (PMID: 29791863)
      Nature. 2017 Feb 9;542(7640):197-202. (PMID: 28114302)
      Nature. 2003 Mar 13;422(6928):198-207. (PMID: 12634793)
      RNA. 2005 Nov;11(11):1640-7. (PMID: 16177138)
      Nat Cell Biol. 2005 Dec;7(12):1261-6. (PMID: 16284623)
      RNA. 2013 Jan;19(1):17-35. (PMID: 23150874)
      J Cell Sci. 2008 Dec 15;121(Pt 24):4134-44. (PMID: 19056672)
      Nat Cell Biol. 2005 Dec;7(12):1267-74. (PMID: 16284622)
      RNA. 2009 Jun;15(6):1059-66. (PMID: 19383768)
      Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13421-6. (PMID: 18755897)
      Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515. (PMID: 30395287)
      Nucleic Acids Res. 2018 Feb 28;46(4):1584-1600. (PMID: 29240946)
      Mol Cell Proteomics. 2014 Dec;13(12):3497-506. (PMID: 25225357)
      Biochem Soc Trans. 2013 Aug;41(4):855-60. (PMID: 23863144)
      Mol Cell. 2011 Oct 7;44(1):120-33. (PMID: 21981923)
      J Am Soc Mass Spectrom. 2018 Jan;29(1):158-173. (PMID: 29080206)
      Mol Cell. 2017 Aug 17;67(4):646-658.e3. (PMID: 28781232)
      Mol Ther. 2016 May;24(5):946-55. (PMID: 26903376)
      RNA. 2009 May;15(5):804-13. (PMID: 19324964)
      Nat Rev Genet. 2013 Jul;14(7):447-59. (PMID: 23732335)
      Nucleic Acids Res. 2016 Jan 29;44(2):524-37. (PMID: 26612865)
      Mol Cell Proteomics. 2014 Sep;13(9):2513-26. (PMID: 24942700)
      Nucleic Acids Res. 2010 Nov;38(21):7736-48. (PMID: 20675357)
      Genes Dev. 2006 Jul 15;20(14):1885-98. (PMID: 16815998)
      Nat Chem Biol. 2005 Oct;1(5):252-62. (PMID: 16408053)
      Nat Methods. 2009 May;6(5):359-62. (PMID: 19377485)
      Nucleic Acids Res. 2015 Sep 3;43(15):7447-61. (PMID: 26170235)
      RNA. 2009 Aug;15(8):1433-42. (PMID: 19535464)
      Cell. 2018 May 3;173(4):946-957.e16. (PMID: 29576456)
      RNA. 2009 Jun;15(6):1078-89. (PMID: 19398495)
      Nature. 2016 Sep 14;537(7620):347-55. (PMID: 27629641)
      Nat Struct Mol Biol. 2011 Oct 07;18(11):1211-7. (PMID: 21984185)
      Nat Struct Mol Biol. 2005 Feb;12(2):133-7. (PMID: 15643423)
      RNA. 2009 May;15(5):781-93. (PMID: 19304925)
    • Grant Information:
      F31 EY030336 United States EY NEI NIH HHS; R35 GM118103 United States GM NIGMS NIH HHS
    • Contributed Indexing:
      Keywords: RNA interference; argonaute; nuclear/cytoplasm localization; trinucleotide repeat containing 6
    • Accession Number:
      0 (AGO2 protein, human)
      0 (Argonaute Proteins)
      0 (Autoantigens)
      0 (MicroRNAs)
      0 (RNA-Binding Proteins)
      0 (TNRC6A protein, human)
      0 (TNRC6B protein, human)
      0 (TNRC6C protein, human)
    • Publication Date:
      Date Created: 20191101 Date Completed: 20200820 Latest Revision: 20210409
    • Publication Date:
      20240104
    • Accession Number:
      PMC6885777
    • Accession Number:
      10.1089/nat.2019.0815
    • Accession Number:
      31670606