Article (Scientific journals)
Selection of hammerhead ribozymes for optimum cleavage of interleukin 6 mRNA.
Hendrix, Chris; Anne, J; Joris, Bernard et al.
1996In Biochemical Journal, 314 ( Pt 2), p. 655-61
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Keywords :
Base Sequence; Interleukin-6/genetics; Kinetics; Molecular Sequence Data; Nucleic Acid Conformation; RNA, Catalytic/chemistry/metabolism; RNA, Messenger/metabolism; Spectrophotometry, Ultraviolet; Substrate Specificity; Temperature
Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Hendrix, Chris
Anne, J
Joris, Bernard ;  Université de Liège - ULiège > Département des sciences de la vie > Physiologie et génétique bactériennes
Van Aerschot, A
Herdewijn, P
Language :
English
Title :
Selection of hammerhead ribozymes for optimum cleavage of interleukin 6 mRNA.
Publication date :
1996
Journal title :
Biochemical Journal
ISSN :
0264-6021
eISSN :
1470-8728
Publisher :
Portland Press, London, United Kingdom
Volume :
314 ( Pt 2)
Pages :
655-61
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 17 May 2012

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