ARA-ATP IMPAIRS 3'-END PROCESSING OF PRE-MESSENGER-RNAS BY INHIBITING BOTH CLEAVAGE AND POLYADENYLATION

被引:11
作者
GHOSHAL, K [1 ]
JACOB, ST [1 ]
机构
[1] CHICAGO MED SCH,DEPT PHARMACOL & MOLEC BIOL,3333 GREEN BAY RD,N CHICAGO,IL 60064
关键词
D O I
10.1093/nar/19.21.5871
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
Previous studies have demonstrated that Ara-ATP can inhibit poly(A) polymerase activity by competing with ATP. To elucidate the mechanism of action of this compound, its effect on the cleavage and polyadenylation of two specific substrates, SV40L and adenovirus L3 pre-mRNAs, was studied in HeLa nuclear extracts. Unlike cordycepin 5' triphosphate, Ara-ATP inhibited both cleavage and poly(A) addition. Addition of poly(A) polymerase fraction devoid of any other factors required for the processing reactions overcame the inhibitory effect on cleavage as well as polyadenylation of pre-mRNAs. These data suggest that Ara-ATP inhibits both cleavage and polyadenylation reactions by interacting with the ATP-binding site on poly(A) polymerase, the activity of which is essential for the cleavage reaction. Ara-ATP also blocked formation of the post-cleavage and polyadenylation-specific complexes, which further confirmed the inhibitory effect of the ATP analog on the two tightly coupled 3'-end processing reactions.
引用
收藏
页码:5871 / 5875
页数:5
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