DNazyme-mediated cleavage of Twist transcripts and increase in cellular apoptosis

被引：28
作者：
Hjiantoniou, E
Iseki, S
Uney, JB
Phylactou, LA
机构：
[1] Cyprus Inst Neurol & Genet, CY-1683 Nicosia, Cyprus
[2] Tokyo Med & Dent Univ, Grad Sch, Sect Mol Craniofacial Embryol, Bunkyo Ku, Tokyo 1138549, Japan
[3] URCN, Bristol BS2 8HW, Avon, England
[4] Univ Bristol, Div Med, MRC Ctr Synapt Plast, Bristol BS2 8HW, Avon, England
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 300卷 / 01期
基金：
英国惠康基金;
关键词：
DNazyme; Twist; apoptosis; basic helix-loop-helix;
D O I：
10.1016/S0006-291X(02)02804-8
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：
DNazymes is a group of catalytic nucleic acids that can be designed to cleave target mRNA molecules in a base-specific way. Twist is a basic helix-loop-helix transcription factor that is involved in the regulation of cellular differentiation and apoptosis. Moreover, it was shown to function in skull development and cause craniosynostosis. DZ-TWT DNuzyme as designed to downregulate Twist expression. The ability of DZ-TWT to cleave mouse Twist mRNA was first shown in a cell-free environment against full-length Twist mRNA. Following transfections of the DZ-TWT in C3H10T1/2 cells a significant reduction of Twist mRNA levels was observed. This was accompanied by a significant rise in p21 mRNA levels. Finally. DZ-TWT transfections resulted in an increase of cellular apoptosis, demonstrating the importance of Twist in apoptotic pathways. These results prove the Usefulness of DNazymes to characterize Twist gene function and further experiments in animals should demonstrate its complete physiological role. (C) 2002 Elsevier Science (USA). All rights reserved.
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页码：178 / 181
页数：4
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