Metal ions: supporting actors in the playbook of small ribozymes.
Metal ions: supporting actors in the playbook of small ribozymes.
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金属离子：小核酶剧本中的辅助演员。
DOI：
10.1039/9781849732512-00175
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Walter NG
中科院分区：
文献类型：
--
作者：
Johnson-Buck AE;McDowell SE;Walter NG
自20世纪80年代以来，已经发现了一些能够进行化学催化的小RNA基序。这些小核酶由大约40至200个核苷酸组成，已被发现在亚病毒和病毒病原体的复制、原核生物中的基因调控中起重要作用，并且最近在非编码真核RNA中被发现。所有已知的天然小核酶-发夹、锤头、丁型肝炎病毒、Varkud卫星和glmS核酶-催化与RNA酶A相同的自切割反应，产生两种产物，一种带有2′-3′环磷酸，另一种带有5′-羟基。虽然最初被认为是专性金属酶，如第I组和第II组自我剪接内含子，但现在已知小核酶支持各种各样的阳离子催化，这些阳离子似乎只是间接参与催化。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是必不可少的，其中最有效的是镁。金属离子主要通过稳定催化活性构象来促进小核酶中的催化作用，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，以及可能通过中和过渡态的负电荷。虽然小的核酶和阳离子之间的相互作用是相对非特异性的，核酶活性是相当敏感的类型和浓度的金属离子存在于溶液中，这表明细胞金属离子的稳态和阳离子的催化RNA的要求，也许在一般的RNA之间的密切的进化关系。
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, 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.