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.
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Van Snick, J. (1990) Annu. Rev. Immunol. 8, 253-278
Hirano, T., Akira, S., Taga, T. and Kishimoto, T. (1990) Immunol. Today 11, 443-449
Wolvekamp, M. C. J. and Marquet, R. L. (1990) Immunol. Lett. 24, 1-10
Bauer, J. and Herrmann, F. (1991) Ann. Hematol. 62, 203-210
Uhlenbeck, O. C. (1987) Nature (London) 328, 596-600
Haseloff, J. and Gerlach, W. L. (1988) Nature (London) 334, 585-591
Ruffner, D. E., Stormo, G. D. and Uhlenbeck, O. C. (1990) Biochemistry 29, 10695-10702
Mahieu, M., Deschuyteneer, R., Forget, D., Vandenbussche, P. and Content, J. (1994) Blood 84, 3758-3765
May, L. T., Helfgott, D. C. and Sehgal, P. B. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 8957-8961
Tang, J. Y., Guo, Q., Roskey, A. and Agrawal, S. (1993) J. Cell. Biochem. 17, 214 (S417)
Hendrix, C., Devreese, B., Rozenski, J., Van Aerschot, A., De Bruyn, A., Van Beeumen, J. and Herdewijn, P. (1995) Nucl. Acids Res. 23, 51-57
Arcone, R., Pucci, P., Zappacosta, F., Fontaine, V., Malorni, A., Marino, G. and Ciliberto, G. (1991) Eur. J. Biochem. 198, 541-547
Fersht, A. (1985) Enzyme structure and mechanism, W. H. Freeman and Co., New York
Heidenreich, O. and Eckstein, F. (1992) J. Biol. Chem. 267, 1904-1909
Heidenreich, O., Benseler, F., Fahrenholz, A. and Eckstein, F. (1994) J. Biol. Chem. 269, 2131-2138
Augustyns, K., Godard, G., Hendrix, C., Van Aerschot, A., Rozenski, J., Saison-Behmoaras, T. and Herdewijn, P. (1993) Nucleic Acids Res. 21, 4670-4676
Zuker, M. (1989) Methods Enzymol. 180, 262-288
Hirano, T., Yasukawa, K., Harada, H., Taga, T., Watanabe, Y., Matsuda, T., Kashiwamura, S., Nakajima, K., Koyama, K., Iwamatsu, A., Tsunasawa, S., Sakiyama, F., Matsui, H., Takahara, Y., Taniguchi, T. and Kishimoto, T. (1986) Nature (London) 324, 73-76
Brakenhoff, J. P. J., de Groot E. R., Evers, R. F., Pannekoek, H. and Aarden, L. A. (1937) J. Immunol. 139, 4116-4121
Heus, H. A. and Pardi, A. (1991) Science 253, 191-194
SantaLucia, J., Jr., Kierzek, R. and Turner, D. H. (1992) Science 256, 217-219
Seela, F. and Kaiser, K. (1987) Nucleic Acids Res. 15, 3113-3129
Temsamani, J., Tang, J.-Y., Padmapriya, A., Kubert, M. and Agrawal, S. (1993) Antisense Res. Dev. 3, 277-284
Hendrix, C., Mahieu, M., Anné, J., Van Calenbergh, S., Van Aerschot, A., Content, J. and Herdewijn, P. (1995) Biochem. Biophys. Res. Commun. 210, 67-73
Zuker, M. and Stiegler, P. (1981) Nucleic Acids Res. 9, 133-148
Cech, T. R., Tanner, N. K., Tinoco, I. Jr., Weir, B. R., Zuker, M. and Perlman, P. S. (1983) Proc. Natl. Acad. Sci. 80, 3903-3907
Freier, S. M., Kierzek, R., Jaeger, J. A., Sugimoto, N., Caruthers, M. H., Neilson, T. and Turner, D. H. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 9373-9377
Saenger, W. (1984) Principles of Nucleic Acid Structure, Springer-Verlag, New York
Plavec, J., Thibaudeau, C. and Chattopadhyaya, J. (1994) J. Am. Chem. Soc. 116, 6558-6560
Fedor, M. J. and Uhlenbeck, O. C. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 1668-1672
Hertel, K. J., Pardi, A., Uhlenbeck, O. C., Koizumi, M., Ohtsuka, E., Uesugi, S., Cedergren, R., Eckstein, F., Gerlach, W. L., Hodgson, R. and Symons, R. H. (1992) Nucleic Acids Res. 20, 3252
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.
