CLEAVAGE OF HUMAN MDR1 MESSENGER-RNA BY A HAMMERHEAD RIBOZYME

被引:25
作者
KOBAYASHI, H
DORAI, T
HOLLAND, JF
OHNUMA, T
机构
[1] CUNY MT SINAI SCH MED,DEPT NEOPLAST DIS,1 GUSTAVE L LEVY PL,BOX 1128,NEW YORK,NY 10029
[2] CUNY MT SINAI SCH MED,DERALD H RUTTENBERG CANC CTR,NEW YORK,NY 10029
关键词
HAMMERHEAD RIBOZYME; MULTIDRUG RESISTANCE;
D O I
10.1016/0014-5793(93)80039-W
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We designed a hammerhead ribozyme which site-specifically cleaved the GUC sequence in codon 179 of MDR1 mRNA. The cleavage site was 6 amino acids upstream from the drug binding site and was considered sufficiently close to the essential locus for P-glycoprotein function. The ribozyme cleaved the MDR1 mRNA under physiological conditions in vitro. The cleavage was dependent on ribozyme concentration and on incubation time. Mg2+ ion was essential for the cleavage. These results show that a potentially useful tool is at hand which may inactivate MDR1 mRNA and revert the multidrug resistance phenotype.
引用
收藏
页码:71 / 74
页数:4
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