Johnson-Buck Alexander E, McDowell Sarah E, Walter Nils G
Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor, MI 48109-1055, USA.
Met Ions Life Sci. 2011;9:175-96. doi: 10.1039/9781849732512-00175.
Since the 1980s, several small RNA motifs capable of chemical catalysis have been discovered. These small ribozymes, composed of between approximately 40 and 200 nucleotides, have been found to play vital roles in the replication of subviral and viral pathogens, as well as in gene regulation in prokaryotes, and have recently been discovered in noncoding eukaryotic RNAs. All of the known natural small ribozymes - the hairpin, hammerhead, hepatitis delta virus, Varkud satellite, and glmS ribozymes--catalyze the same self-cleavage reaction as RNase A, resulting in two products, one bearing a 2'-3' cyclic phosphate and the other a 5'-hydroxyl group. Although originally thought to be obligate metalloenzymes like the group I and II self-splicing introns, the small ribozymes are now known to support catalysis in a wide variety of cations that appear to be only indirectly involved in catalysis. Nevertheless, under physiologic conditions, metal ions are essential for the proper folding and function of the small ribozymes, the most effective of these being magnesium. Metal ions contribute to catalysis in the small ribozymes primarily by stabilizing the catalytically active conformation, but in some cases also by activating RNA functional groups for catalysis, directly participating in catalytic acid-base chemistry, and perhaps by neutralizing the developing negative charge of the transition state. Although interactions between the small ribozymes and cations are relatively nonspecific, ribozyme activity is quite sensitive to the types and concentrations of metal ions present in solution, suggesting a close evolutionary relationship between cellular metal ion homeostasis and cation requirements of catalytic RNAs, and perhaps RNA in general.
自20世纪80年代以来，人们发现了几种能够进行化学催化的小RNA基序。这些由大约40至200个核苷酸组成的小核酶，在亚病毒和病毒病原体的复制以及原核生物的基因调控中发挥着至关重要的作用，最近还在非编码真核RNA中被发现。所有已知的天然小核酶——发夹核酶、锤头核酶、丁型肝炎病毒核酶、Varkud卫星核酶和glmS核酶——都催化与核糖核酸酶A相同的自我切割反应，产生两种产物，一种带有2'-3'环磷酸酯，另一种带有5'-羟基。尽管最初认为小核酶像I类和II类自我剪接内含子一样是专一性金属酶，但现在已知它们能在多种似乎仅间接参与催化的阳离子中支持催化作用。然而，在生理条件下，金属离子对于小核酶的正确折叠和功能至关重要，其中最有效的是镁。金属离子在小核酶中促进催化作用主要是通过稳定催化活性构象，但在某些情况下也通过激活RNA官能团进行催化、直接参与催化酸碱化学过程，或许还通过中和过渡态不断增加的负电荷来实现。尽管小核酶与阳离子之间的相互作用相对非特异性，但核酶活性对溶液中存在的金属离子类型和浓度非常敏感，这表明细胞金属离子稳态与催化RNA（或许一般而言是RNA）的阳离子需求之间存在密切的进化关系。
