Selection of hammerhead ribozymes for optimum cleavage of interleukin 6 mRNA.
Identifieur interne : 002609 ( PubMed/Checkpoint ); précédent : 002608; suivant : 002610Selection of hammerhead ribozymes for optimum cleavage of interleukin 6 mRNA.
Auteurs : C. Hendrix [Belgique] ; J. Anné ; B. Joris ; A. Van Aerschot ; P. HerdewijnSource :
- The Biochemical journal [ 0264-6021 ] ; 1996.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , chemistry : RNA, Catalytic.
- chemical , genetics : Interleukin-6.
- chemical , metabolism : RNA, Catalytic, RNA, Messenger.
- Base Sequence, Kinetics, Molecular Sequence Data, Nucleic Acid Conformation, Spectrophotometry, Ultraviolet, Substrate Specificity, Temperature.
Abstract
Four GUC triplets in the coding region of the MRNA of interleukin 6 (IL-6) were examined for their suitabilty to serve as a target for hammerhead ribozome-mediated cleavage. This selection procedure was performed with the intention to downregulate IL-6 production as a potential treatment of those diseases in which IL-6 overexpression is involved. Hammerhead ribozymes and their respective short synthetic substrates (19-mers) were synthesized for these four GUC triplets. Notwithstanding the identical catalytic core sequences, the difference in base composition of the helices involved in substrate binding caused substantial variation in cleavage activity. The cleavage reactions on the 1035 nucleotide IL-6 mRNA transcript revealed that two ribozymes were able to cleave this substrate, showing a decrease in catalytic efficiency to 1/30 and 1/300 of the short substrate. This study indicates that the GUC triplet located at nucleotide 510 of the mRNA of IL-6 is the best site for hammerhead ribozyme-mediated cleavage. We suggest that in future targeting of chemically modified hammerhead ribosomes for cleavage of IL-6 RNA should be directed at this location.
DOI: 10.1042/bj3140655
PubMed: 8670082
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
pubmed:8670082Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Selection of hammerhead ribozymes for optimum cleavage of interleukin 6 mRNA.</title><author><name sortKey="Hendrix, C" sort="Hendrix, C" uniqKey="Hendrix C" first="C" last="Hendrix">C. Hendrix</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory for Medicinal Chemistry, Rega Instiute, Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory for Medicinal Chemistry, Rega Instiute, Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation></author><author><name sortKey="Anne, J" sort="Anne, J" uniqKey="Anne J" first="J" last="Anné">J. Anné</name></author><author><name sortKey="Joris, B" sort="Joris, B" uniqKey="Joris B" first="B" last="Joris">B. Joris</name></author><author><name sortKey="Van Aerschot, A" sort="Van Aerschot, A" uniqKey="Van Aerschot A" first="A" last="Van Aerschot">A. Van Aerschot</name></author><author><name sortKey="Herdewijn, P" sort="Herdewijn, P" uniqKey="Herdewijn P" first="P" last="Herdewijn">P. Herdewijn</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1996">1996</date><idno type="RBID">pubmed:8670082</idno><idno type="pmid">8670082</idno><idno type="doi">10.1042/bj3140655</idno><idno type="wicri:Area/PubMed/Corpus">002782</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002782</idno><idno type="wicri:Area/PubMed/Curation">002782</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002782</idno><idno type="wicri:Area/PubMed/Checkpoint">002609</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002609</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Selection of hammerhead ribozymes for optimum cleavage of interleukin 6 mRNA.</title><author><name sortKey="Hendrix, C" sort="Hendrix, C" uniqKey="Hendrix C" first="C" last="Hendrix">C. Hendrix</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory for Medicinal Chemistry, Rega Instiute, Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory for Medicinal Chemistry, Rega Instiute, Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation></author><author><name sortKey="Anne, J" sort="Anne, J" uniqKey="Anne J" first="J" last="Anné">J. Anné</name></author><author><name sortKey="Joris, B" sort="Joris, B" uniqKey="Joris B" first="B" last="Joris">B. Joris</name></author><author><name sortKey="Van Aerschot, A" sort="Van Aerschot, A" uniqKey="Van Aerschot A" first="A" last="Van Aerschot">A. Van Aerschot</name></author><author><name sortKey="Herdewijn, P" sort="Herdewijn, P" uniqKey="Herdewijn P" first="P" last="Herdewijn">P. Herdewijn</name></author></analytic><series><title level="j">The Biochemical journal</title><idno type="ISSN">0264-6021</idno><imprint><date when="1996" type="published">1996</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Base Sequence</term><term>Interleukin-6 (genetics)</term><term>Kinetics</term><term>Molecular Sequence Data</term><term>Nucleic Acid Conformation</term><term>RNA, Catalytic (chemistry)</term><term>RNA, Catalytic (metabolism)</term><term>RNA, Messenger (metabolism)</term><term>Spectrophotometry, Ultraviolet</term><term>Substrate Specificity</term><term>Temperature</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN catalytique ()</term><term>ARN catalytique (métabolisme)</term><term>ARN messager (métabolisme)</term><term>Cinétique</term><term>Conformation d'acide nucléique</term><term>Données de séquences moléculaires</term><term>Interleukine-6 (génétique)</term><term>Spectrophotométrie UV</term><term>Spécificité du substrat</term><term>Séquence nucléotidique</term><term>Température</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>RNA, Catalytic</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Interleukin-6</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>RNA, Catalytic</term><term>RNA, Messenger</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Interleukine-6</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN catalytique</term><term>ARN messager</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Base Sequence</term><term>Kinetics</term><term>Molecular Sequence Data</term><term>Nucleic Acid Conformation</term><term>Spectrophotometry, Ultraviolet</term><term>Substrate Specificity</term><term>Temperature</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ARN catalytique</term><term>Cinétique</term><term>Conformation d'acide nucléique</term><term>Données de séquences moléculaires</term><term>Spectrophotométrie UV</term><term>Spécificité du substrat</term><term>Séquence nucléotidique</term><term>Température</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Four GUC triplets in the coding region of the MRNA of interleukin 6 (IL-6) were examined for their suitabilty to serve as a target for hammerhead ribozome-mediated cleavage. This selection procedure was performed with the intention to downregulate IL-6 production as a potential treatment of those diseases in which IL-6 overexpression is involved. Hammerhead ribozymes and their respective short synthetic substrates (19-mers) were synthesized for these four GUC triplets. Notwithstanding the identical catalytic core sequences, the difference in base composition of the helices involved in substrate binding caused substantial variation in cleavage activity. The cleavage reactions on the 1035 nucleotide IL-6 mRNA transcript revealed that two ribozymes were able to cleave this substrate, showing a decrease in catalytic efficiency to 1/30 and 1/300 of the short substrate. This study indicates that the GUC triplet located at nucleotide 510 of the mRNA of IL-6 is the best site for hammerhead ribozyme-mediated cleavage. We suggest that in future targeting of chemically modified hammerhead ribosomes for cleavage of IL-6 RNA should be directed at this location.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">8670082</PMID><DateCompleted><Year>1996</Year><Month>08</Month><Day>05</Day></DateCompleted><DateRevised><Year>2019</Year><Month>05</Month><Day>01</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0264-6021</ISSN><JournalIssue CitedMedium="Print"><Volume>314 ( Pt 2)</Volume><PubDate><Year>1996</Year><Month>Mar</Month><Day>01</Day></PubDate></JournalIssue><Title>The Biochemical journal</Title><ISOAbbreviation>Biochem. J.</ISOAbbreviation></Journal><ArticleTitle>Selection of hammerhead ribozymes for optimum cleavage of interleukin 6 mRNA.</ArticleTitle><Pagination><MedlinePgn>655-61</MedlinePgn></Pagination><Abstract><AbstractText>Four GUC triplets in the coding region of the MRNA of interleukin 6 (IL-6) were examined for their suitabilty to serve as a target for hammerhead ribozome-mediated cleavage. This selection procedure was performed with the intention to downregulate IL-6 production as a potential treatment of those diseases in which IL-6 overexpression is involved. Hammerhead ribozymes and their respective short synthetic substrates (19-mers) were synthesized for these four GUC triplets. Notwithstanding the identical catalytic core sequences, the difference in base composition of the helices involved in substrate binding caused substantial variation in cleavage activity. The cleavage reactions on the 1035 nucleotide IL-6 mRNA transcript revealed that two ribozymes were able to cleave this substrate, showing a decrease in catalytic efficiency to 1/30 and 1/300 of the short substrate. This study indicates that the GUC triplet located at nucleotide 510 of the mRNA of IL-6 is the best site for hammerhead ribozyme-mediated cleavage. We suggest that in future targeting of chemically modified hammerhead ribosomes for cleavage of IL-6 RNA should be directed at this location.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hendrix</LastName><ForeName>C</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Laboratory for Medicinal Chemistry, Rega Instiute, Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Anné</LastName><ForeName>J</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Joris</LastName><ForeName>B</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Van Aerschot</LastName><ForeName>A</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Herdewijn</LastName><ForeName>P</ForeName><Initials>P</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Biochem J</MedlineTA><NlmUniqueID>2984726R</NlmUniqueID><ISSNLinking>0264-6021</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015850">Interleukin-6</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016337">RNA, Catalytic</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012333">RNA, Messenger</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D001483" MajorTopicYN="N">Base Sequence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015850" MajorTopicYN="N">Interleukin-6</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007700" MajorTopicYN="N">Kinetics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008969" MajorTopicYN="N">Molecular Sequence Data</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009690" MajorTopicYN="N">Nucleic Acid Conformation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016337" MajorTopicYN="N">RNA, Catalytic</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012333" MajorTopicYN="N">RNA, Messenger</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013056" MajorTopicYN="N">Spectrophotometry, Ultraviolet</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013379" MajorTopicYN="N">Substrate Specificity</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013696" MajorTopicYN="N">Temperature</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1996</Year><Month>3</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1996</Year><Month>3</Month><Day>1</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1996</Year><Month>3</Month><Day>1</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">8670082</ArticleId><ArticleId IdType="pmc">PMC1217097</ArticleId><ArticleId IdType="doi">10.1042/bj3140655</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Nucleic Acids Res. 1981 Jan 10;9(1):133-48</Citation><ArticleIdList><ArticleId IdType="pubmed">6163133</ArticleId></ArticleIdList></Reference><Reference><Citation>Biochem Biophys Res Commun. 1995 May 5;210(1):67-73</Citation><ArticleIdList><ArticleId IdType="pubmed">7741750</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 1986 Nov 6-12;324(6092):73-6</Citation><ArticleIdList><ArticleId IdType="pubmed">3491322</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 1986 Dec;83(23):8957-61</Citation><ArticleIdList><ArticleId IdType="pubmed">3538015</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 1986 Dec;83(24):9373-7</Citation><ArticleIdList><ArticleId IdType="pubmed">2432595</ArticleId></ArticleIdList></Reference><Reference><Citation>Nucleic Acids Res. 1987 Apr 10;15(7):3113-29</Citation><ArticleIdList><ArticleId IdType="pubmed">3562246</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 1987 Aug 13-19;328(6131):596-600</Citation><ArticleIdList><ArticleId IdType="pubmed">2441261</ArticleId></ArticleIdList></Reference><Reference><Citation>J Immunol. 1987 Dec 15;139(12):4116-21</Citation><ArticleIdList><ArticleId IdType="pubmed">3320204</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 1988 Aug 18;334(6183):585-91</Citation><ArticleIdList><ArticleId IdType="pubmed">2457170</ArticleId></ArticleIdList></Reference><Reference><Citation>Methods Enzymol. 1989;180:262-88</Citation><ArticleIdList><ArticleId IdType="pubmed">2482418</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 1990 Mar;87(5):1668-72</Citation><ArticleIdList><ArticleId IdType="pubmed">1689847</ArticleId></ArticleIdList></Reference><Reference><Citation>Annu Rev Immunol. 1990;8:253-78</Citation><ArticleIdList><ArticleId IdType="pubmed">2188664</ArticleId></ArticleIdList></Reference><Reference><Citation>Immunol Lett. 1990 Mar-Apr;24(1):1-9</Citation><ArticleIdList><ArticleId IdType="pubmed">2197219</ArticleId></ArticleIdList></Reference><Reference><Citation>Biochemistry. 1990 Nov 27;29(47):10695-702</Citation><ArticleIdList><ArticleId IdType="pubmed">1703005</ArticleId></ArticleIdList></Reference><Reference><Citation>Immunol Today. 1990 Dec;11(12):443-9</Citation><ArticleIdList><ArticleId IdType="pubmed">2127356</ArticleId></ArticleIdList></Reference><Reference><Citation>Eur J Biochem. 1991 Jun 15;198(3):541-7</Citation><ArticleIdList><ArticleId IdType="pubmed">2050135</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 1991 Jul 12;253(5016):191-4</Citation><ArticleIdList><ArticleId IdType="pubmed">1712983</ArticleId></ArticleIdList></Reference><Reference><Citation>Ann Hematol. 1991 Jun;62(6):203-10</Citation><ArticleIdList><ArticleId IdType="pubmed">1854882</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 1992 Jan 25;267(3):1904-9</Citation><ArticleIdList><ArticleId IdType="pubmed">1730726</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 1992 Apr 10;256(5054):217-9</Citation><ArticleIdList><ArticleId IdType="pubmed">1373521</ArticleId></ArticleIdList></Reference><Reference><Citation>Nucleic Acids Res. 1992 Jun 25;20(12):3252</Citation><ArticleIdList><ArticleId IdType="pubmed">1620624</ArticleId></ArticleIdList></Reference><Reference><Citation>Nucleic Acids Res. 1993 Oct 11;21(20):4670-6</Citation><ArticleIdList><ArticleId IdType="pubmed">7694231</ArticleId></ArticleIdList></Reference><Reference><Citation>Antisense Res Dev. 1993 Fall;3(3):277-84</Citation><ArticleIdList><ArticleId IdType="pubmed">8286928</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 1994 Jan 21;269(3):2131-8</Citation><ArticleIdList><ArticleId IdType="pubmed">8294467</ArticleId></ArticleIdList></Reference><Reference><Citation>Blood. 1994 Dec 1;84(11):3758-65</Citation><ArticleIdList><ArticleId IdType="pubmed">7949132</ArticleId></ArticleIdList></Reference><Reference><Citation>Nucleic Acids Res. 1995 Jan 11;23(1):51-7</Citation><ArticleIdList><ArticleId IdType="pubmed">7870590</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 1983 Jul;80(13):3903-7</Citation><ArticleIdList><ArticleId IdType="pubmed">6306649</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>Belgique</li></country></list><tree><noCountry><name sortKey="Anne, J" sort="Anne, J" uniqKey="Anne J" first="J" last="Anné">J. Anné</name><name sortKey="Herdewijn, P" sort="Herdewijn, P" uniqKey="Herdewijn P" first="P" last="Herdewijn">P. Herdewijn</name><name sortKey="Joris, B" sort="Joris, B" uniqKey="Joris B" first="B" last="Joris">B. Joris</name><name sortKey="Van Aerschot, A" sort="Van Aerschot, A" uniqKey="Van Aerschot A" first="A" last="Van Aerschot">A. Van Aerschot</name></noCountry><country name="Belgique"><noRegion><name sortKey="Hendrix, C" sort="Hendrix, C" uniqKey="Hendrix C" first="C" last="Hendrix">C. Hendrix</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/PubMed/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002609 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd -nk 002609 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= PubMed
|étape= Checkpoint
|type= RBID
|clé= pubmed:8670082
|texte= Selection of hammerhead ribozymes for optimum cleavage of interleukin 6 mRNA.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/RBID.i -Sk "pubmed:8670082" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |