Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase

The N7-methylguanosine (m7G) cap is the defining structural feature of eukaryotic mRNAs. Most eukaryotic viruses that replicate in the cytoplasm, including coronaviruses, have evolved strategies to cap their RNAs. In this report, we used a yeast genetic system to functionally screen for the cap-form...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 106; no. 9; pp. 3484 - 3489
Main Authors Chen, Yu, Cai, Hui, Pan, Ji'an, Xiang, Nian, Tien, Po, Ahola, Tero, Guo, Deyin
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 03.03.2009
National Acad Sciences
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Abstract The N7-methylguanosine (m7G) cap is the defining structural feature of eukaryotic mRNAs. Most eukaryotic viruses that replicate in the cytoplasm, including coronaviruses, have evolved strategies to cap their RNAs. In this report, we used a yeast genetic system to functionally screen for the cap-forming enzymes encoded by severe acute respiratory syndrome (SARS) coronavirus and identified the nonstructural protein (nsp) 14 of SARS coronavirus as a (guanine-N7)-methyltransferase (N7-MTase) in vivo in yeast cells and in vitro using purified enzymes and RNA substrates. Interestingly, coronavirus nsp14 was previously characterized as a 3'-to-5' exoribonuclease, and by mutational analysis, we mapped the N7-MTase domain to the carboxy-terminal part of nsp14 that shows features conserved with cellular N7-MTase in structure-based sequence alignment. The exoribonuclease active site was dispensable but the exoribonuclease domain was required for N7-MTase activity. Such combination of the 2 functional domains in coronavirus nsp14 suggests that it may represent a novel form of RNA-processing enzymes. Mutational analysis in a replicon system showed that the N7-MTase activity was important for SARS virus replication/transcription and can thus be used as an attractive drug target to develop antivirals for control of coronaviruses including the deadly SARS virus. Furthermore, the observation that the N7-MTase of RNA life could function in lieu of that in DNA life provides interesting evolutionary insight and practical possibilities in antiviral drug screening.
AbstractList The N7-methylguanosine (m7G) cap is the defining structural feature of eukaryotic mRNAs. Most eukaryotic viruses that replicate in the cytoplasm, including coronaviruses, have evolved strategies to cap their RNAs. In this report, we used a yeast genetic system to functionally screen for the cap-forming enzymes encoded by severe acute respiratory syndrome (SARS) coronavirus and identified the nonstructural protein (nsp) 14 of SARS coronavirus as a (guanine-N7)-methyltransferase (N7-MTase) in vivo in yeast cells and in vitro using purified enzymes and RNA substrates. Interestingly, coronavirus nsp14 was previously characterized as a 3′-to-5′ exoribonuclease, and by mutational analysis, we mapped the N7-MTase domain to the carboxy-terminal part of nsp14 that shows features conserved with cellular N7-MTase in structure-based sequence alignment. The exoribonuclease active site was dispensable but the exoribonuclease domain was required for N7-MTase activity. Such combination of the 2 functional domains in coronavirus nsp14 suggests that it may represent a novel form of RNA-processing enzymes. Mutational analysis in a replicon system showed that the N7-MTase activity was important for SARS virus replication/transcription and can thus be used as an attractive drug target to develop antivirals for control of coronaviruses including the deadly SARS virus. Furthermore, the observation that the N7-MTase of RNA life could function in lieu of that in DNA life provides interesting evolutionary insight and practical possibilities in antiviral drug screening.
The N7-methylguanosine (m7G) cap is the defining structural feature of eukaryotic mRNAs. Most eukaryotic viruses that replicate in the cytoplasm, including coronaviruses, have evolved strategies to cap their RNAs. In this report, we used a yeast genetic system to functionally screen for the cap-forming enzymes encoded by severe acute respiratory syndrome (SARS) coronavirus and identified the nonstructural protein (nsp) 14 of SARS coronavirus as a (guanine-N7)-methyltransferase (N7-MTase) in vivo in yeast cells and in vitro using purified enzymes and RNA substrates. Interestingly, coronavirus nsp14 was previously characterized as a 3'-to-5' exoribonuclease, and by mutational analysis, we mapped the N7-MTase domain to the carboxy-terminal part of nsp14 that shows features conserved with cellular N7-MTase in structure-based sequence alignment. The exoribonuclease active site was dispensable but the exoribonuclease domain was required for N7-MTase activity. Such combination of the 2 functional domains in coronavirus nsp14 suggests that it may represent a novel form of RNA-processing enzymes. Mutational analysis in a replicon system showed that the N7-MTase activity was important for SARS virus replication/transcription and can thus be used as an attractive drug target to develop antivirals for control of coronaviruses including the deadly SARS virus. Furthermore, the observation that the N7-MTase of RNA life could function in lieu of that in DNA life provides interesting evolutionary insight and practical possibilities in antiviral drug screening. [PUBLICATION ABSTRACT]
The N7-methylguanosine (m7G) cap is the defining structural feature of eukaryotic mRNAs. Most eukaryotic viruses that replicate in the cytoplasm, including corona viruses, have evolved strategies to cap their RNAs. In this report, we used a yeast genetic system to functionally screen for the cap-forming enzymes encoded by severe acute respiratory syndrome (SARS) coronavirus and identified the nonstructural protein (nsp) 14 of SARS coronavirus as a (guanine-N7)-methyltransferase (N7-MTase) in vivo in yeast cells and in vitro using purified enzymes and RNA substrates. Interestingly, coronavirus nsp14 was previously characterized as a 3'-to-5' exoribonuclease, and by mutational analysis, we mapped the N7-MTase domain to the carboxy-terminal part of nsp14 that shows features conserved with cellular N7-MTase in structurebased sequence alignment. The exoribonuclease active site was dispensable but the exoribonuclease domain was required for N7-MTase activity. Such combination of the 2 functional domains in coronavirus nsp14 suggests that it may represent a novel form of RNA-processing enzymes. Mutational analysis in a replicon system showed that the N7-MTase activity was important for SARS virus replication/transcription and can thus be used as an attractive drug target to develop antivirals for control of coronaviruses including the deadly SARS virus. Furthermore, the observation that the N7-MTase of RNA life could function in lieu of that in DNA life provides interesting evolutionary insight and practical possibilities in antiviral drug screening.
Author Ahola, Tero
Pan, Ji'an
Guo, Deyin
Chen, Yu
Tien, Po
Cai, Hui
Xiang, Nian
Author_xml – sequence: 1
  fullname: Chen, Yu
– sequence: 2
  fullname: Cai, Hui
– sequence: 3
  fullname: Pan, Ji'an
– sequence: 4
  fullname: Xiang, Nian
– sequence: 5
  fullname: Tien, Po
– sequence: 6
  fullname: Ahola, Tero
– sequence: 7
  fullname: Guo, Deyin
BackLink https://www.ncbi.nlm.nih.gov/pubmed/19208801$$D View this record in MEDLINE/PubMed
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Cites_doi 10.1128/JVI.78.11.5619-5632.2004
10.1371/journal.pbio.0060226
10.1371/journal.pone.0003299
10.1073/pnas.0403127101
10.1016/S0959-440X(02)00391-3
10.4161/cc.5.20.3361
10.1128/JVI.00407-08
10.1093/nar/gnh007
10.1128/JVI.02704-06
10.1186/1472-6807-5-19
10.1073/pnas.0508200103
10.1128/JVI.00385-06
10.1128/JVI.01296-07
10.1128/JVI.74.12.5486-5494.2000
10.1128/JVI.79.9.5288-5295.2005
10.1128/JVI.77.13.7300-7307.2003
10.1074/jbc.274.23.16553
10.1128/JVI.79.6.3391-3400.2005
10.1128/JVI.02455-06
10.1016/S0022-2836(03)00865-9
10.1016/j.molcel.2006.11.013
10.1371/journal.ppat.0010039
10.1016/S0065-3527(00)55003-9
10.1073/pnas.0509821103
10.1128/jvi.38.2.661-670.1981
10.1056/NEJMoa030747
10.1128/JVI.00814-06
10.1093/emboj/cdf635
10.1073/pnas.92.2.507
10.1016/S0092-8674(03)00424-0
10.1128/jvi.71.1.392-397.1997
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References 15731233 - J Virol. 2005 Mar;79(6):3391-400
12504684 - Curr Opin Struct Biol. 2002 Dec;12(6):783-93
18417574 - J Virol. 2008 Aug;82(16):8071-84
6165837 - J Virol. 1981 May;38(2):661-70
11050942 - Adv Virus Res. 2000;55:135-84
12805428 - J Virol. 2003 Jul;77(13):7300-7
12809601 - Cell. 2003 Jun 13;113(6):701-2
15140959 - J Virol. 2004 Jun;78(11):5619-32
14744982 - Nucleic Acids Res. 2004;32(1):e14
10347220 - J Biol Chem. 1999 Jun 4;274(23):16553-62
16709677 - Proc Natl Acad Sci U S A. 2006 May 30;103(22):8493-8
17804504 - J Virol. 2007 Nov;81(22):12135-44
16928748 - J Virol. 2006 Nov;80(21):10900-6
8985362 - J Virol. 1997 Jan;71(1):392-7
16341254 - PLoS Pathog. 2005 Dec;1(4):e39
17301144 - J Virol. 2007 May;81(9):4412-21
17927896 - J Biochem Mol Biol. 2007 Sep 30;40(5):649-55
12690091 - N Engl J Med. 2003 May 15;348(20):1967-76
18798692 - PLoS Biol. 2008 Sep 16;6(9):e226
15304651 - Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12694-9
16912287 - J Virol. 2006 Sep;80(17):8362-70
16225687 - BMC Struct Biol. 2005;5:19
15827143 - J Virol. 2005 May;79(9):5288-95
18827877 - PLoS One. 2008;3(10):e3299
10823853 - J Virol. 2000 Jun;74(12):5486-94
12927536 - J Mol Biol. 2003 Aug 29;331(5):991-1004
17267492 - J Virol. 2007 Apr;81(8):3891-903
17218273 - Mol Cell. 2007 Jan 12;25(1):85-97
16549795 - Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5108-13
17102613 - Cell Cycle. 2006 Oct;5(20):2414-6
7831320 - Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):507-11
12456663 - EMBO J. 2002 Dec 2;21(23):6571-80
Chen P (e_1_3_3_7_2) 2007; 40
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  doi: 10.1128/JVI.78.11.5619-5632.2004
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  doi: 10.1371/journal.pbio.0060226
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  doi: 10.1073/pnas.0403127101
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  doi: 10.1016/S0959-440X(02)00391-3
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  doi: 10.4161/cc.5.20.3361
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  doi: 10.1128/JVI.00407-08
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  doi: 10.1093/nar/gnh007
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  doi: 10.1128/JVI.02704-06
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  doi: 10.1186/1472-6807-5-19
– ident: e_1_3_3_8_2
  doi: 10.1073/pnas.0508200103
– ident: e_1_3_3_28_2
  doi: 10.1128/JVI.00385-06
– ident: e_1_3_3_29_2
  doi: 10.1128/JVI.01296-07
– ident: e_1_3_3_18_2
  doi: 10.1128/JVI.74.12.5486-5494.2000
– ident: e_1_3_3_19_2
  doi: 10.1128/JVI.79.9.5288-5295.2005
– ident: e_1_3_3_17_2
  doi: 10.1128/JVI.77.13.7300-7307.2003
– volume: 40
  start-page: 649
  year: 2007
  ident: e_1_3_3_7_2
  article-title: Biochemical characterization of exoribonuclease encoded by SARS coronavirus
  publication-title: J Biochem Mol Biol
  contributor:
    fullname: Chen P
– ident: e_1_3_3_16_2
  doi: 10.1074/jbc.274.23.16553
– ident: e_1_3_3_31_2
  doi: 10.1128/JVI.79.6.3391-3400.2005
– ident: e_1_3_3_21_2
  doi: 10.1128/JVI.02455-06
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  doi: 10.1016/S0022-2836(03)00865-9
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  doi: 10.1016/j.molcel.2006.11.013
– ident: e_1_3_3_30_2
  doi: 10.1371/journal.ppat.0010039
– ident: e_1_3_3_1_2
  doi: 10.1016/S0065-3527(00)55003-9
– ident: e_1_3_3_3_2
  doi: 10.1073/pnas.0509821103
– ident: e_1_3_3_10_2
  doi: 10.1128/jvi.38.2.661-670.1981
– ident: e_1_3_3_5_2
  doi: 10.1056/NEJMoa030747
– ident: e_1_3_3_20_2
  doi: 10.1128/JVI.00814-06
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  doi: 10.1093/emboj/cdf635
– ident: e_1_3_3_4_2
  doi: 10.1073/pnas.92.2.507
– ident: e_1_3_3_13_2
  doi: 10.1016/S0092-8674(03)00424-0
– ident: e_1_3_3_24_2
  doi: 10.1128/jvi.71.1.392-397.1997
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Snippet The N7-methylguanosine (m7G) cap is the defining structural feature of eukaryotic mRNAs. Most eukaryotic viruses that replicate in the cytoplasm, including...
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SubjectTerms Biological Sciences
Coronavirus
Enzymes
Eukaryotes
Exons
Gene Deletion
Genome, Viral - genetics
Guanosine - analogs & derivatives
Guanosine - metabolism
Messenger RNA
Methyltransferases - genetics
Methyltransferases - metabolism
Mutation
Mutation - genetics
Plasmids
Polymerase chain reaction
Protein Binding
Proteins
Ribonucleic acid
RNA
SARS coronavirus
SARS virus
SARS Virus - enzymology
SARS Virus - genetics
Severe acute respiratory syndrome
Transcription, Genetic - genetics
Viral Nonstructural Proteins - genetics
Viral Nonstructural Proteins - metabolism
Virus Replication
Viruses
Yeasts
Title Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase
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http://www.pnas.org/content/106/9/3484.abstract
https://www.ncbi.nlm.nih.gov/pubmed/19208801
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