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Multiple myeloma-associated hDIS3 mutations cause perturbations in cellular RNA metabolism and suggest hDIS3 PIN domain as a potential drug target.
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- معلومة اضافية
- المصدر:
Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
- بيانات النشر:
Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
- الموضوع:
- نبذة مختصرة :
hDIS3 is a mainly nuclear, catalytic subunit of the human exosome complex, containing exonucleolytic (RNB) and endonucleolytic (PIN) active domains. Mutations in hDIS3 have been found in ∼10% of patients with multiple myeloma (MM). Here, we show that these mutations interfere with hDIS3 exonucleolytic activity. Yeast harboring corresponding mutations in DIS3 show growth inhibition and changes in nuclear RNA metabolism typical for exosome dysfunction. Construction of a conditional DIS3 knockout in the chicken DT40 cell line revealed that DIS3 is essential for cell survival, indicating that its function cannot be replaced by other exosome-associated nucleases: hDIS3L and hRRP6. Moreover, HEK293-derived cells, in which depletion of endogenous wild-type hDIS3 was complemented with exogenously expressed MM hDIS3 mutants, proliferate at a slower rate and exhibit aberrant RNA metabolism. Importantly, MM mutations are synthetically lethal with the hDIS3 PIN domain catalytic mutation both in yeast and human cells. Since mutations in PIN domain alone have little effect on cell physiology, our results predict the hDIS3 PIN domain as a potential drug target for MM patients with hDIS3 mutations. It is an interesting example of intramolecular synthetic lethality with putative therapeutic potential in humans.
- References:
EMBO J. 2010 Jul 21;29(14):2342-57. (PMID: 20531386)
Blood. 2012 Aug 2;120(5):1077-86. (PMID: 22573403)
Nature. 2013 Mar 7;495(7439):70-5. (PMID: 23376952)
RNA. 2008 Nov;14(11):2305-13. (PMID: 18824516)
Nature. 2011 Mar 24;471(7339):467-72. (PMID: 21430775)
Science. 2008 Dec 19;322(5909):1851-4. (PMID: 19056938)
Science. 2011 Jan 28;331(6016):435-9. (PMID: 21163964)
Cancer Res. 1997 Mar 1;57(5):921-5. (PMID: 9041195)
Cell. 2005 Jun 3;121(5):725-37. (PMID: 15935759)
Nature. 2012 Jan 11;481(7382):506-10. (PMID: 22237025)
EMBO J. 1999 Oct 1;18(19):5399-410. (PMID: 10508172)
J Biol Chem. 2009 Jul 31;284(31):20486-98. (PMID: 19458082)
Cell. 2006 Dec 15;127(6):1223-37. (PMID: 17174896)
J Intern Med. 2011 Feb;269(2):137-47. (PMID: 21158983)
Annu Rev Med. 2011;62:249-64. (PMID: 21090965)
Genes Dev. 2004 Jun 1;18(11):1227-40. (PMID: 15145828)
EMBO Rep. 2010 Dec;11(12):936-42. (PMID: 21072061)
Genetics. 2012 Jul;191(3):671-702. (PMID: 22785621)
Nucleic Acids Res. 2000 Apr 15;28(8):1684-91. (PMID: 10734186)
Nat Genet. 2012 Feb 05;44(3):277-84. (PMID: 22306653)
Methods. 2001 Jul;24(3):218-29. (PMID: 11403571)
EMBO J. 2002 Jan 15;21(1-2):165-74. (PMID: 11782436)
Cancer Res. 2013 Mar 15;73(6):2003-13. (PMID: 23319804)
Cell. 2009 Oct 30;139(3):547-59. (PMID: 19879841)
Nature. 2008 Dec 18;456(7224):993-6. (PMID: 19060886)
Nat Struct Mol Biol. 2007 Jan;14(1):15-22. (PMID: 17173052)
Nature. 2005 Apr 14;434(7035):917-21. (PMID: 15829967)
Curr Med Chem. 2012;19(23):3858-73. (PMID: 22788762)
Cell. 1991 Oct 4;67(1):179-88. (PMID: 1913816)
EMBO J. 2013 Jul 3;32(13):1842-54. (PMID: 23503588)
Nature. 2005 Apr 14;434(7035):913-7. (PMID: 15829966)
Mol Cell. 2012 Oct 12;48(1):133-44. (PMID: 22902556)
Biochim Biophys Acta. 2008 Sep;1779(9):558-65. (PMID: 18313413)
Mol Cell. 2004 Jun 4;14(5):571-83. (PMID: 15175153)
RNA. 2008 Jan;14(1):107-16. (PMID: 18000032)
Nucleic Acids Res. 2009 Mar;37(4):1127-40. (PMID: 19129231)
Mol Cell. 2012 Nov 9;48(3):422-33. (PMID: 23000172)
Genes Dev. 2007 Aug 1;21(15):1833-56. (PMID: 17671086)
Cell. 2011 Feb 4;144(3):353-63. (PMID: 21255825)
Nucleic Acids Res. 2013 Apr 1;41(6):3845-58. (PMID: 23404585)
EMBO J. 2013 Jul 3;32(13):1855-68. (PMID: 23756462)
Trends Biochem Sci. 2008 Oct;33(10):501-10. (PMID: 18786828)
Biotechniques. 2010 Jun;48(6):463-5. (PMID: 20569222)
Nat Methods. 2007 Mar;4(3):251-6. (PMID: 17293868)
J Pathol. 2013 Feb;229(3):422-9. (PMID: 23165508)
Mol Cell. 2008 Mar 28;29(6):717-28. (PMID: 18374646)
Mol Cell. 2012 Nov 9;48(3):409-21. (PMID: 23000176)
EMBO J. 2010 Jul 21;29(14):2358-67. (PMID: 20531389)
Anal Biochem. 2005 Nov 15;346(2):210-6. (PMID: 16212928)
Mol Cell. 2011 Aug 19;43(4):624-37. (PMID: 21855801)
J Virol Methods. 2006 Aug;135(2):157-62. (PMID: 16600391)
Wiley Interdiscip Rev RNA. 2013 Sep-Oct;4(5):607-15. (PMID: 23776156)
BMC Cancer. 2013 Apr 03;13:178. (PMID: 23551967)
Subcell Biochem. 2006;40:347-9. (PMID: 17623917)
Chembiochem. 2010 May 3;11(7):938-45. (PMID: 20301164)
Cancer Res. 2011 Apr 1;71(7):2561-71. (PMID: 21343389)
N Engl J Med. 2011 Mar 17;364(11):1046-60. (PMID: 21410373)
BMC Biotechnol. 2001;1:7. (PMID: 11591226)
RNA Biol. 2011 Jan-Feb;8(1):61-6. (PMID: 21289487)
Mol Cell. 2007 Jul 20;27(2):324-31. (PMID: 17643380)
Nature. 2006 Sep 7;443(7107):110-4. (PMID: 16957732)
RNA. 2005 Apr;11(4):459-69. (PMID: 15703439)
Nature. 2013 May 9;497(7448):244-8. (PMID: 23594738)
Nat Struct Mol Biol. 2009 Jan;16(1):56-62. (PMID: 19060898)
Cancer Invest. 2007 Sep;25(6):427-34. (PMID: 17882654)
- الرقم المعرف:
0 (Saccharomyces cerevisiae Proteins)
63231-63-0 (RNA)
EC 3.1.- (Exosome Multienzyme Ribonuclease Complex)
EC 3.1.13.- (DIS3 protein, S cerevisiae)
EC 3.1.13.- (DIS3 protein, human)
- الموضوع:
Date Created: 20131024 Date Completed: 20140325 Latest Revision: 20211021
- الموضوع:
20231215
- الرقم المعرف:
PMC3902924
- الرقم المعرف:
10.1093/nar/gkt930
- الرقم المعرف:
24150935
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