DNazyme-mediated cleavage of Twist transcripts and increase in cellular apoptosis
DNazyme-mediated cleavage of Twist transcripts and increase in cellular apoptosis
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DOI：
10.1016/s0006-291x(02)02804-8
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发表时间：
2003-01-03
影响因子：
3.1
通讯作者：
Phylactou, LA
中科院分区：
文献类型：
--
作者：
Hjiantoniou, E;Iseki, S;Phylactou, LA
DNAzymes是一组催化核酸，可以被设计为以碱基特异性方式切割靶mRNA分子。Twist是一种基本的螺旋-环-螺旋转录因子，参与细胞分化和凋亡的调节。此外，它被证明在头骨发育中起作用，并导致颅缝早闭。DZ-TWT DNuzyme被设计为下调Twist表达。DZ-TWT切割小鼠Twist mRNA的能力首先在无细胞环境中针对全长Twist mRNA显示。在C3 H10 T1/2细胞中转染DZ-TWT后，观察到Twist mRNA水平显著降低。这伴随着p21 mRNA水平的显著升高。终于来了DZ-TWT转染导致细胞凋亡的增加，表明Twist在凋亡途径中的重要性。这些结果证明了DNAzymes对描述Twist基因功能的准确性，进一步的动物实验将证明其完整的生理作用。(C)2002年爱思唯尔科学（美国）。All rights reserved.
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.