Cell：华人学者解析RNA被降解过程

　　

生物通报道：核糖核酸酶Ⅲ（RNaseⅢ）家族是一类识别特定序列对双链RNA进行切割的内切酶，切割后一般产物3'末端会带有两个碱基的粘性末端。目前RNaseⅢ家族研究得最多的是在RNA干扰途径中起重要作用的Dicer酶，它负责切割双链双链RNA后产生小干扰RNA；而结构较简单的细菌RNaseⅢ则是作为这一类酶的介绍典型。

来自美国国立健康研究院癌症研究中心的华人学者吉新华（音译：Ji Xinhua）带领的研究小组，第一次解开了RNaseⅢ与产物结合复合物的晶体结构，文章发表在1月26日的Cell杂志上。

研究人员利用经过突变后酶活性有所降低的RNaseⅢ进行研究，对酶进行催化的活性部位的三级结构进行了研究，从而进一步解释了RNaseⅢ进行切割时的机制。研究发现，在蛋白中7个残基的接头（linker）帮助蛋白与RNA直接的识别。在RNaseⅢ中确定了四类的RNA结合基元（motif），在dsRNA中确定有三个相互作用盒。保守的氨基酸残基和二价阳离子负责断裂键。对这些水解RNA机制的了解可以进一步推广到其它RNaseⅢ家族的成员中（生物通记者 谢菲）。

（图片来源：Cell）

原文连接：Structural Insight into the Mechanism of Double-Stranded RNA Processing by Ribonuclease III，Volume 124, Issue 2, 27 January 2006, Pages 355-366.

Ji Xinhua简介：

Xinhua Ji began his career taking care of the basic medical needs of a small village in Northeast China. With only a high school education and a basic knowledge of chemistry, which he had gleaned from his classes, he became responsible for the health care of 1,000 people who lived in the small town. What started out in China as a career in medicine has led Dr. Ji to a quest, one that searches out cancer cells in the human body, and then seeks ways to kill those cells, leaving the healthy ones to thrive.

Dr. Ji heads the Biomolecular Structure Section at the National Cancer Institute (NCI), Center for Cancer Research (CCR), which is a part of the Macromolecular Crystallography Laboratory, headed by Dr. Alexander Wlodawer. According to Dr. Ji, his research “addresses the structure and function of biomolecular systems of anticancer and/or antimicrobial significance and explores the feasibility of structure-based drug design, targeting such biomolecules. In collaboration with Dr. Larry Keefer here at NCI-Frederick, and Dr. Shivendra Singh of the University of Pittsburgh, we have been able to develop a new family of anticancer pro-drug molecules.” These new pro-drugs are activated by an enzyme inside cancer cells, which releases nitric oxide to kill the cells or inhibit their growth without damaging healthy cells. A patent for this research was granted in Australia in 2001, in the United States in 2003, and just this year in Europe.