The Center for the Molecular Biology of RNA, Sinsheimer Laboratories, University of California at Santa Cruz, Santa Cruz, California, USA.
Prog Mol Biol Transl Sci. 2013;120:1-23. doi: 10.1016/B978-0-12-381286-5.00001-9.
The hammerhead ribozyme has long been considered a prototype for understanding RNA catalysis, but discrepancies between the earlier crystal structures of a minimal hammerhead self-cleaving motif and various biochemical investigations frustrated attempt to understand hammerhead ribozyme catalysis in terms of structure. With the discovery that a tertiary contact distal from the ribozyme's active site greatly enhances its catalytic prowess, and the emergence of new corresponding crystal structures of full-length hammerhead ribozymes, a unified understanding of catalysis in terms of the structure is now possible. A mechanism in which the invariant residue G12 functions as a general base, and the 2'-OH moiety of the invariant G8, itself forming a tertiary base pair with the invariant C3, is the general acid, appears consistent with both the crystal structure and biochemical experimental results. Originally discovered in the context of plant satellite RNA viruses, the hammerhead more recently has been found embedded in the 3'-untranslated region of mature mammalian mRNAs, suggesting additional biological roles in genetic regulation.
锤头核酶长期以来一直被认为是理解 RNA 催化作用的原型，但早期最小锤头自我切割基序的晶体结构与各种生化研究之间存在差异，这使得人们难以根据结构来理解锤头核酶的催化作用。随着发现在远离核酶活性部位的三级接触大大增强了其催化能力，以及全长锤头核酶的新对应晶体结构的出现，现在有可能根据结构来统一理解催化作用。一种机制是，不变残基 G12 作为通用碱基，而不变 G8 的 2'-OH 部分与不变 C3 形成三级碱基对，充当通用酸，这与晶体结构和生化实验结果都一致。锤头核酶最初是在植物卫星 RNA 病毒的背景下发现的，最近在成熟哺乳动物 mRNA 的 3'-非翻译区中也发现了它，这表明它在基因调控中具有额外的生物学作用。
