Filipowicz W, Billy E, Drabikowski K, Genschik P
Friedrich Miescher-Institut, Basel, Switzerland.
Acta Biochim Pol. 1998;45(4):895-906.
The 2',3'-cyclic phosphate termini are produced, as either intermediates or final products, during RNA cleavage by many different endoribonucleases. Likewise, ribozymes such as hammerheads, hairpins, or the hepatitis delta ribozyme, generate 2',3'-cyclic phosphate ends. Discovery of the RNA 3'-terminal phosphate cyclase has indicated that cyclic phosphate termini in RNA can also be produced by an entirely different mechanism. The RNA 3'-phosphate cyclase converts the 3'-terminal phosphate in RNA into the 2',3'-cyclic phosphodiester in the ATP-dependent reaction which involves formation of the covalent cyclase-AMP and the RNA-N3' pp5' A intermediates. The findings that several eukaryotic and prokaryotic RNA ligases require the 2',3'-cyclic phosphate for the ligation of RNA molecules raised a possibility that the RNA 3'-phosphate cyclase may have an anabolic function in RNA metabolism by generating terminal cyclic groups required for ligation. Recent cloning of a cDNA encoding the human cyclase indicated that genes encoding cyclase-like proteins are conserved among Eucarya, Bacteria, and Archaea. The protein encoded by the Escherichia coli gene was overexpressed and shown to have the RNA 3'-phosphate cyclase activity. This article reviews properties of the human and bacterial cyclases, their mechanism of action and substrate specificity. Possible biological functions of the enzymes are also discussed.
在许多不同的核糖核酸内切酶切割RNA的过程中，2',3'-环磷酸末端作为中间产物或最终产物产生。同样，诸如锤头状、发夹状或丁型肝炎病毒核酶等核酶也会产生2',3'-环磷酸末端。RNA 3'-末端磷酸环化酶的发现表明，RNA中的环磷酸末端也可以通过一种完全不同的机制产生。RNA 3'-磷酸环化酶在依赖ATP的反应中将RNA中的3'-末端磷酸转化为2',3'-环磷酸二酯，该反应涉及共价环化酶-AMP和RNA-N3' pp5' A中间产物的形成。几种真核和原核RNA连接酶在连接RNA分子时需要2',3'-环磷酸这一发现，提出了一种可能性，即RNA 3'-磷酸环化酶可能通过生成连接所需的末端环基团，在RNA代谢中具有合成代谢功能。最近克隆的编码人环化酶的cDNA表明，编码环化酶样蛋白的基因在真核生物、细菌和古细菌中是保守的。大肠杆菌基因编码的蛋白质被过度表达，并显示具有RNA 3'-磷酸环化酶活性。本文综述了人和细菌环化酶的特性、它们的作用机制和底物特异性。还讨论了这些酶可能的生物学功能。
