دورية أكاديمية
أعرض في EDS

The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan.

التفاصيل البيبلوغرافية
العنوان: The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan.
المؤلفون: Mittal N; Computational and Systems Biology, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056, Basel, Switzerland. nitish.mittal@unibas.ch., Guimaraes JC; Computational and Systems Biology, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056, Basel, Switzerland., Gross T; Growth and Development, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056, Basel, Switzerland., Schmidt A; Proteomics Core Facility, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056, Basel, Switzerland., Vina-Vilaseca A; Computational and Systems Biology, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056, Basel, Switzerland., Nedialkova DD; Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Strasse 54, 48149, Münster, Germany., Aeschimann F; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4002, Basel, Switzerland., Leidel SA; Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Strasse 54, 48149, Münster, Germany.; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149, Muenster, Germany.; Faculty of Medicine, University of Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany., Spang A; Growth and Development, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056, Basel, Switzerland., Zavolan M; Computational and Systems Biology, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056, Basel, Switzerland. mihaela.zavolan@unibas.ch.
المصدر: Nature communications [Nat Commun] 2017 Sep 06; Vol. 8 (1), pp. 457. Date of Electronic Publication: 2017 Sep 06.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Protein Biosynthesis*, Basic-Leucine Zipper Transcription Factors/*metabolism , Saccharomyces cerevisiae/*metabolism , Saccharomyces cerevisiae/*physiology , Saccharomyces cerevisiae Proteins/*metabolism, Gene Expression Regulation, Fungal ; Genes, Fungal ; Open Reading Frames/genetics ; Ribosomes/metabolism ; Saccharomyces cerevisiae/genetics ; Up-Regulation/genetics
مستخلص: In Saccharomyces cerevisiae, deletion of large ribosomal subunit protein-encoding genes increases the replicative lifespan in a Gcn4-dependent manner. However, how Gcn4, a key transcriptional activator of amino acid biosynthesis genes, increases lifespan, is unknown. Here we show that Gcn4 acts as a repressor of protein synthesis. By analyzing the messenger RNA and protein abundance, ribosome occupancy and protein synthesis rate in various yeast strains, we demonstrate that Gcn4 is sufficient to reduce protein synthesis and increase yeast lifespan. Chromatin immunoprecipitation reveals Gcn4 binding not only at genes that are activated, but also at genes, some encoding ribosomal proteins, that are repressed upon Gcn4 overexpression. The promoters of repressed genes contain Rap1 binding motifs. Our data suggest that Gcn4 is a central regulator of protein synthesis under multiple perturbations, including ribosomal protein gene deletions, calorie restriction, and rapamycin treatment, and provide an explanation for its role in longevity and stress response.The transcription factor Gcn4 is known to regulate yeast amino acid synthesis. Here, the authors show that Gcn4 also acts as a repressor of protein biosynthesis in a range of conditions that enhance yeast lifespan, such as ribosomal protein knockout, calorie restriction or mTOR inhibition.
References: Nat Rev Genet. 2014 Dec;15(12 ):829-45. (PMID: 25365966)
Mol Syst Biol. 2011 Nov 08;7:549. (PMID: 22068332)
Nat Rev Mol Cell Biol. 2012 May 23;13(6):355-69. (PMID: 22617470)
Nat Protoc. 2013 Mar;8(3):539-54. (PMID: 23429716)
Mol Cell Biol. 1991 Jun;11(6):3203-16. (PMID: 2038326)
Science. 2009 Apr 10;324(5924):218-23. (PMID: 19213877)
EMBO J. 2011 Mar 2;30(5):859-72. (PMID: 21183953)
Ageing Res Rev. 2011 Apr;10(2):225-37. (PMID: 20385253)
Genome Biol. 2011 Dec 21;12(12):R125. (PMID: 22189060)
Methods Enzymol. 1991;194:3-21. (PMID: 2005794)
Mol Cell. 2011 Feb 18;41(4):480-92. (PMID: 21329885)
Nat Med. 2015 Dec;21(12):1416-23. (PMID: 26646498)
Nucleic Acids Res. 2012 Jan;40(Database issue):D169-79. (PMID: 22102575)
Microbiology. 2002 Apr;148(Pt 4):1081-90. (PMID: 11932453)
PLoS Biol. 2004 Aug;2(8):E246. (PMID: 15314660)
Yeast. 1994 Dec;10(13):1793-808. (PMID: 7747518)
Genetics. 2011 Dec;189(4):1177-201. (PMID: 22174183)
Science. 2005 Nov 18;310(5751):1193-6. (PMID: 16293764)
Physiol Genomics. 2000 Aug 09;3(2):83-92. (PMID: 11015603)
Wiley Interdiscip Rev RNA. 2016 Mar-Apr;7(2):198-212. (PMID: 26732699)
Mol Cell Biol. 2007 Sep;27(17):5968-85. (PMID: 17548477)
Mol Biol Cell. 2000 Dec;11(12):4241-57. (PMID: 11102521)
Mol Cell Biol. 2000 Apr;20(8):2706-17. (PMID: 10733573)
Nat Genet. 2007 May;39(5):683-7. (PMID: 17417638)
Aging Cell. 2007 Feb;6(1):111-9. (PMID: 17266680)
Science. 2008 Jun 6;320(5881):1344-9. (PMID: 18451266)
Science. 2016 Jan 29;351(6272):aad3867. (PMID: 26823435)
Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11269-74. (PMID: 15277680)
Cell. 2015 Jun 18;161(7):1606-18. (PMID: 26052047)
Adv Exp Med Biol. 2010;694:14-29. (PMID: 20886753)
BMC Bioinformatics. 2006 Mar 07;7:113. (PMID: 16522208)
Nature. 2004 Sep 2;431(7004):99-104. (PMID: 15343339)
Yeast. 1998 Mar 30;14(5):471-7. (PMID: 9559554)
Nat Protoc. 2012 Jul 26;7(8):1534-50. (PMID: 22836135)
Nat Biotechnol. 2010 Sep;28(9):970-5. (PMID: 20802496)
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W202-8. (PMID: 19458158)
Nature. 1959 Jun 20;183(4677):1751-2. (PMID: 13666896)
Genome Biol. 2008;9(9):R137. (PMID: 18798982)
Annu Rev Microbiol. 2005;59:407-50. (PMID: 16153175)
Genes Dev. 2005 Jul 1;19(13):1544-55. (PMID: 15998808)
Cell Metab. 2015 Nov 3;22(5):895-906. (PMID: 26456335)
Cell. 2008 Apr 18;133(2):292-302. (PMID: 18423200)
PLoS Comput Biol. 2009 Sep;5(9):e1000502. (PMID: 19750212)
Data Brief. 2015 Sep 04;5:297-304. (PMID: 26550600)
J Vis Exp. 2009 Jun 25;(28):null. (PMID: 19556967)
Proc Int Conf Intell Syst Mol Biol. 1994;2:28-36. (PMID: 7584402)
J Proteome Res. 2016 Aug 5;15(8):2537-47. (PMID: 27345528)
Aging Cell. 2014 Dec;13(6):1012-8. (PMID: 25156122)
Aging Cell. 2013 Feb;12(1):156-66. (PMID: 23167605)
Exp Gerontol. 2007 Apr;42(4):275-86. (PMID: 17174052)
Mol Cell Biol. 2001 Jul;21(13):4347-68. (PMID: 11390663)
Nat Cell Biol. 2013 May;15(5):481-90. (PMID: 23624402)
Nature. 2012 Apr 11;484(7393):251-5. (PMID: 22498630)
Aging Cell. 2007 Feb;6(1):95-110. (PMID: 17266679)
Science. 2010 Apr 16;328(5976):321-6. (PMID: 20395504)
Nat Commun. 2014 Nov 21;5:5465. (PMID: 25413384)
Cell. 2000 Oct 13;103(2):253-62. (PMID: 11057898)
J Gerontol A Biol Sci Med Sci. 2015 Mar;70(3):263-72. (PMID: 24691093)
Science. 2012 Feb 3;335(6068):552-7. (PMID: 22194413)
Cell Metab. 2010 Jun 9;11(6):453-65. (PMID: 20519118)
Anal Chem. 2003 Sep 1;75(17):4646-58. (PMID: 14632076)
Cell. 2015 Jan 29;160(3):477-88. (PMID: 25619689)
J Neurosci. 2013 Feb 6;33(6):2398-407. (PMID: 23392669)
J Bacteriol. 2001 Apr;183(7):2331-4. (PMID: 11244074)
Nat Genet. 2001 Aug;28(4):327-34. (PMID: 11455386)
Mol Cell Biol. 2013 Dec;33(24):4811-23. (PMID: 24100011)
Nat Rev Genet. 2007 Nov;8(11):835-44. (PMID: 17909538)
Genome Res. 2008 Apr;18(4):564-70. (PMID: 18340043)
Yeast. 2005 Jan 15;22(1):1-12. (PMID: 15565729)
Biochem Soc Trans. 2006 Feb;34(Pt 1):7-11. (PMID: 16246168)
Cell. 1990 Jun 29;61(7):1199-208. (PMID: 2163758)
Science. 1996 Jul 5;273(5271):54-9. (PMID: 8658195)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
المشرفين على المادة: 0 (Basic-Leucine Zipper Transcription Factors)
0 (GCN4 protein, S cerevisiae)
0 (Saccharomyces cerevisiae Proteins)
تواريخ الأحداث: Date Created: 20170908 Date Completed: 20180108 Latest Revision: 20220408
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC5587724
DOI: 10.1038/s41467-017-00539-y
PMID: 28878244
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-017-00539-y