The highly conserved KEOPS/EKC complex is essential for a universal tRNA modification, t6A
The highly conserved Kinase, Endopeptidase and Other Proteins of small Size (KEOPS)/Endopeptidase‐like and Kinase associated to transcribed Chromatin (EKC) protein complex has been implicated in transcription, telomere maintenance and chromosome segregation, but its exact function remains unknown. T...
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| Veröffentlicht in: | The EMBO journal 2011-03, Vol.30 (5), p.873-881 |
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| creator | Srinivasan, Madhusudhan Mehta, Preeti Yu, Yao Prugar, Evelyn Koonin, Eugene V Karzai, A Wali Sternglanz, Rolf |
| description | The highly conserved Kinase, Endopeptidase and Other Proteins of small Size (KEOPS)/Endopeptidase‐like and Kinase associated to transcribed Chromatin (EKC) protein complex has been implicated in transcription, telomere maintenance and chromosome segregation, but its exact function remains unknown. The complex consists of five proteins, Kinase‐Associated Endopeptidase (Kae1), a highly conserved protein present in bacteria, archaea and eukaryotes, a kinase (Bud32) and three additional small polypeptides. We showed that the complex is required for a universal tRNA modification, threonyl carbamoyl adenosine (t6A), found in all tRNAs that pair with ANN codons in mRNA. We also showed that the bacterial ortholog of Kae1, YgjD, is required for t6A modification of
Escherichia coli
tRNAs. The ATPase activity of Kae1 and the kinase activity of Bud32 are required for the modification. The yeast protein Sua5 has been reported previously to be required for t6A synthesis. Using yeast extracts, we established an
in vitro
system for the synthesis of t6A that requires Sua5, Kae1, threonine, bicarbonate and ATP. It remains to be determined whether all reported defects of KEOPS/EKC mutants can be attributed to the lack of t6A, or whether the complex has multiple functions.
The Endopeptidase‐like and Kinase associated to transcribed Chromatin (KEOPS)/Endopeptidase‐like and Kinase associated to transcribed Chromatin (EKC) complex has been implicated in multiple biological processes including transcription, telomere maintenance and chromosome segregation. This study reveals a role in the biosynthesis of a universal tRNA modification threonyl carbamoyl adenosine (t6A). |
| doi_str_mv | 10.1038/emboj.2010.343 |
| format | Article |
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Escherichia coli
tRNAs. The ATPase activity of Kae1 and the kinase activity of Bud32 are required for the modification. The yeast protein Sua5 has been reported previously to be required for t6A synthesis. Using yeast extracts, we established an
in vitro
system for the synthesis of t6A that requires Sua5, Kae1, threonine, bicarbonate and ATP. It remains to be determined whether all reported defects of KEOPS/EKC mutants can be attributed to the lack of t6A, or whether the complex has multiple functions.
The Endopeptidase‐like and Kinase associated to transcribed Chromatin (KEOPS)/Endopeptidase‐like and Kinase associated to transcribed Chromatin (EKC) complex has been implicated in multiple biological processes including transcription, telomere maintenance and chromosome segregation. This study reveals a role in the biosynthesis of a universal tRNA modification threonyl carbamoyl adenosine (t6A).</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1038/emboj.2010.343</identifier><identifier>PMID: 21183954</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Adenosine - analogs & derivatives ; Adenosine - metabolism ; Amino Acid Sequence ; Archaea ; ATP ; Base Sequence ; Cellular biology ; Chromatin ; E coli ; Kae1 ; KEOPS-EKC complex ; Kinases ; Metalloendopeptidases - genetics ; Metalloendopeptidases - metabolism ; Molecular biology ; Molecular Sequence Data ; Multiprotein Complexes ; Nucleic Acid Conformation ; Protein Biosynthesis ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; Proteins ; Ribonucleic acid ; RNA ; RNA, Transfer - chemistry ; RNA, Transfer - genetics ; RNA, Transfer - metabolism ; Saccharomyces cerevisiae - genetics ; Saccharomyces cerevisiae - growth & development ; Saccharomyces cerevisiae - metabolism ; Saccharomyces cerevisiae Proteins - genetics ; Saccharomyces cerevisiae Proteins - metabolism ; Sequence Homology, Amino Acid ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Sua5 ; t6A ; tRNA ; Yeasts</subject><ispartof>The EMBO journal, 2011-03, Vol.30 (5), p.873-881</ispartof><rights>European Molecular Biology Organization 2011</rights><rights>Copyright © 2011 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group Mar 2, 2011</rights><rights>Copyright © 2011, European Molecular Biology Organization 2011 European Molecular Biology Organization</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6293-3dc63dc20b99d06714c5b3720f1c7ac65e927d5d6209fadfe358a7fdb176478e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049205/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049205/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1416,1432,27923,27924,41119,42188,45573,45574,46408,46832,51575,53790,53792</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1038/emboj.2010.343$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21183954$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Srinivasan, Madhusudhan</creatorcontrib><creatorcontrib>Mehta, Preeti</creatorcontrib><creatorcontrib>Yu, Yao</creatorcontrib><creatorcontrib>Prugar, Evelyn</creatorcontrib><creatorcontrib>Koonin, Eugene V</creatorcontrib><creatorcontrib>Karzai, A Wali</creatorcontrib><creatorcontrib>Sternglanz, Rolf</creatorcontrib><title>The highly conserved KEOPS/EKC complex is essential for a universal tRNA modification, t6A</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>The highly conserved Kinase, Endopeptidase and Other Proteins of small Size (KEOPS)/Endopeptidase‐like and Kinase associated to transcribed Chromatin (EKC) protein complex has been implicated in transcription, telomere maintenance and chromosome segregation, but its exact function remains unknown. The complex consists of five proteins, Kinase‐Associated Endopeptidase (Kae1), a highly conserved protein present in bacteria, archaea and eukaryotes, a kinase (Bud32) and three additional small polypeptides. We showed that the complex is required for a universal tRNA modification, threonyl carbamoyl adenosine (t6A), found in all tRNAs that pair with ANN codons in mRNA. We also showed that the bacterial ortholog of Kae1, YgjD, is required for t6A modification of
Escherichia coli
tRNAs. The ATPase activity of Kae1 and the kinase activity of Bud32 are required for the modification. The yeast protein Sua5 has been reported previously to be required for t6A synthesis. Using yeast extracts, we established an
in vitro
system for the synthesis of t6A that requires Sua5, Kae1, threonine, bicarbonate and ATP. It remains to be determined whether all reported defects of KEOPS/EKC mutants can be attributed to the lack of t6A, or whether the complex has multiple functions.
The Endopeptidase‐like and Kinase associated to transcribed Chromatin (KEOPS)/Endopeptidase‐like and Kinase associated to transcribed Chromatin (EKC) complex has been implicated in multiple biological processes including transcription, telomere maintenance and chromosome segregation. This study reveals a role in the biosynthesis of a universal tRNA modification threonyl carbamoyl adenosine (t6A).</description><subject>Adenosine - analogs & derivatives</subject><subject>Adenosine - metabolism</subject><subject>Amino Acid Sequence</subject><subject>Archaea</subject><subject>ATP</subject><subject>Base Sequence</subject><subject>Cellular biology</subject><subject>Chromatin</subject><subject>E coli</subject><subject>Kae1</subject><subject>KEOPS-EKC complex</subject><subject>Kinases</subject><subject>Metalloendopeptidases - genetics</subject><subject>Metalloendopeptidases - metabolism</subject><subject>Molecular biology</subject><subject>Molecular Sequence Data</subject><subject>Multiprotein Complexes</subject><subject>Nucleic Acid Conformation</subject><subject>Protein Biosynthesis</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proteins</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Transfer - chemistry</subject><subject>RNA, Transfer - genetics</subject><subject>RNA, Transfer - metabolism</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Saccharomyces cerevisiae - growth & development</subject><subject>Saccharomyces cerevisiae - metabolism</subject><subject>Saccharomyces cerevisiae Proteins - genetics</subject><subject>Saccharomyces cerevisiae Proteins - metabolism</subject><subject>Sequence Homology, Amino Acid</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>Sua5</subject><subject>t6A</subject><subject>tRNA</subject><subject>Yeasts</subject><issn>0261-4189</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kUuP0zAUhS0EYsrAliWy2MCCTP2I7XiDVEoZYIZ5wADSbCwncVqXJC52Uqb_HrcdWkCIhWVd-7vnXp0DwGOMjjCi2dA0uZsfERRrmtI7YIBTjhKCBLsLBohwnKQ4kwfgQQhzhBDLBL4PDgjGGZUsHYDrq5mBMzud1StYuDYYvzQlPJmcX3waTk7G8a1Z1OYG2gBNCKbtrK5h5TzUsG_t0vgQ6-7j2Qg2rrSVLXRnXfsCdnz0ENyrdB3Mo9v7EHx-M7kav01Oz4_fjUenScGJpAktCx4PQbmUJeICpwXLqSCowoXQBWdGElGykhMkK11WhrJMi6rMseCpyAw9BC-3uos-b0xZxCW9rtXC20b7lXLaqj9_WjtTU7dUFKWSIBYFnt0KePe9N6FTjQ2FqWvdGtcHlTEWDaVcRPL5f8lofkYZJimN6NO_0LnrfRuNiHppirmQMkJPfl99t_OvfCIgtsAPW5vV7h8jtU5fbdJX6_RVTF9NPrx6vy7oZv5w2xliUzs1fj__3937jVvd9d7shm2wvWyyhWzozM2O0f6biv4Ipr6eHUfJ19eXlxdflKQ_ATKEzN4</recordid><startdate>20110302</startdate><enddate>20110302</enddate><creator>Srinivasan, Madhusudhan</creator><creator>Mehta, Preeti</creator><creator>Yu, Yao</creator><creator>Prugar, Evelyn</creator><creator>Koonin, Eugene V</creator><creator>Karzai, A Wali</creator><creator>Sternglanz, Rolf</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><general>Nature Publishing Group</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110302</creationdate><title>The highly conserved KEOPS/EKC complex is essential for a universal tRNA modification, t6A</title><author>Srinivasan, Madhusudhan ; Mehta, Preeti ; Yu, Yao ; Prugar, Evelyn ; Koonin, Eugene V ; Karzai, A Wali ; Sternglanz, Rolf</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6293-3dc63dc20b99d06714c5b3720f1c7ac65e927d5d6209fadfe358a7fdb176478e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adenosine - analogs & derivatives</topic><topic>Adenosine - metabolism</topic><topic>Amino Acid Sequence</topic><topic>Archaea</topic><topic>ATP</topic><topic>Base Sequence</topic><topic>Cellular biology</topic><topic>Chromatin</topic><topic>E coli</topic><topic>Kae1</topic><topic>KEOPS-EKC complex</topic><topic>Kinases</topic><topic>Metalloendopeptidases - genetics</topic><topic>Metalloendopeptidases - metabolism</topic><topic>Molecular biology</topic><topic>Molecular Sequence Data</topic><topic>Multiprotein Complexes</topic><topic>Nucleic Acid Conformation</topic><topic>Protein Biosynthesis</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Proteins</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Transfer - chemistry</topic><topic>RNA, Transfer - genetics</topic><topic>RNA, Transfer - metabolism</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Saccharomyces cerevisiae - growth & development</topic><topic>Saccharomyces cerevisiae - metabolism</topic><topic>Saccharomyces cerevisiae Proteins - genetics</topic><topic>Saccharomyces cerevisiae Proteins - metabolism</topic><topic>Sequence Homology, Amino Acid</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</topic><topic>Sua5</topic><topic>t6A</topic><topic>tRNA</topic><topic>Yeasts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Srinivasan, Madhusudhan</creatorcontrib><creatorcontrib>Mehta, Preeti</creatorcontrib><creatorcontrib>Yu, Yao</creatorcontrib><creatorcontrib>Prugar, Evelyn</creatorcontrib><creatorcontrib>Koonin, Eugene V</creatorcontrib><creatorcontrib>Karzai, A Wali</creatorcontrib><creatorcontrib>Sternglanz, Rolf</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Srinivasan, Madhusudhan</au><au>Mehta, Preeti</au><au>Yu, Yao</au><au>Prugar, Evelyn</au><au>Koonin, Eugene V</au><au>Karzai, A Wali</au><au>Sternglanz, Rolf</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The highly conserved KEOPS/EKC complex is essential for a universal tRNA modification, t6A</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2011-03-02</date><risdate>2011</risdate><volume>30</volume><issue>5</issue><spage>873</spage><epage>881</epage><pages>873-881</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>The highly conserved Kinase, Endopeptidase and Other Proteins of small Size (KEOPS)/Endopeptidase‐like and Kinase associated to transcribed Chromatin (EKC) protein complex has been implicated in transcription, telomere maintenance and chromosome segregation, but its exact function remains unknown. The complex consists of five proteins, Kinase‐Associated Endopeptidase (Kae1), a highly conserved protein present in bacteria, archaea and eukaryotes, a kinase (Bud32) and three additional small polypeptides. We showed that the complex is required for a universal tRNA modification, threonyl carbamoyl adenosine (t6A), found in all tRNAs that pair with ANN codons in mRNA. We also showed that the bacterial ortholog of Kae1, YgjD, is required for t6A modification of
Escherichia coli
tRNAs. The ATPase activity of Kae1 and the kinase activity of Bud32 are required for the modification. The yeast protein Sua5 has been reported previously to be required for t6A synthesis. Using yeast extracts, we established an
in vitro
system for the synthesis of t6A that requires Sua5, Kae1, threonine, bicarbonate and ATP. It remains to be determined whether all reported defects of KEOPS/EKC mutants can be attributed to the lack of t6A, or whether the complex has multiple functions.
The Endopeptidase‐like and Kinase associated to transcribed Chromatin (KEOPS)/Endopeptidase‐like and Kinase associated to transcribed Chromatin (EKC) complex has been implicated in multiple biological processes including transcription, telomere maintenance and chromosome segregation. This study reveals a role in the biosynthesis of a universal tRNA modification threonyl carbamoyl adenosine (t6A).</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>21183954</pmid><doi>10.1038/emboj.2010.343</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenosine - analogs & derivatives Adenosine - metabolism Amino Acid Sequence Archaea ATP Base Sequence Cellular biology Chromatin E coli Kae1 KEOPS-EKC complex Kinases Metalloendopeptidases - genetics Metalloendopeptidases - metabolism Molecular biology Molecular Sequence Data Multiprotein Complexes Nucleic Acid Conformation Protein Biosynthesis Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Proteins Ribonucleic acid RNA RNA, Transfer - chemistry RNA, Transfer - genetics RNA, Transfer - metabolism Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - growth & development Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins - genetics Saccharomyces cerevisiae Proteins - metabolism Sequence Homology, Amino Acid Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Sua5 t6A tRNA Yeasts |
| title | The highly conserved KEOPS/EKC complex is essential for a universal tRNA modification, t6A |
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