Abstract
Fourteen well-defined ribozyme classes have been identified to date, among which nine are site-specific self-cleaving ribozymes. Very recently, small self-cleaving ribozymes have attracted renewed interest in their structure, biochemistry, and biological function since the discovery, during the last three years, of four novel ribozymes, termed twister, twister sister, pistol, and hatchet. In this review, we mainly address the structure, biochemistry, and catalytic mechanism of the novel ribozymes. They are characterized by distinct active site architectures and divergent, but similar, biochemical properties. The cleavage activities of the ribozymes are highly dependent upon divalent cations, pH, and base-specific mutations, which can cause changes in the nucleotide arrangement and/or electrostatic potential around the cleavage site. It is most likely that a guanine and adenine in close proximity of the cleavage site are involved in general acid-base catalysis. In addition, metal ions appear to play a structural rather than catalytic role although some of their crystal structures have shown a direct metal ion coordination to a non-bridging phosphate oxygen at the cleavage site. Collectively, the structural and biochemical data of the four newest ribozymes could contribute to advance our mechanistic understanding of how self-cleaving ribozymes accomplish their efficient site-specific RNA cleavages.
Highlights
RNA catalysts, termed ribozymes, are presumed to have existed as abundant cellular components that served a wide variety of biological functions, as well as acting as carriers of genetic information, in the “RNA world” era before the emergence of protein enzymes [1,2]
Structural and mutational data of the O. sativa twister suggest that the higher pKa is derived primarily from residue G45, and G45 N1, which is close to the U6 O20, acts as general base for activation/deprotonation of the nucleophile for attack at the phosphorus center during the cleavage reaction (γ catalysis) [28,30]
The results showed that the two divalent metal ions have similar impacts on the cleavage activity, suggesting that metals cannot be coordinated directly to the active site of twister ribozyme
Summary
RNA catalysts, termed ribozymes, are presumed to have existed as abundant cellular components that served a wide variety of biological functions, as well as acting as carriers of genetic information, in the “RNA world” era before the emergence of protein enzymes [1,2]. The nucleolytic ribozymes include hairpin [19], hammerhead [20,21], hepatitis delta virus (HDV)-like [22], glucosamine-6-phosphate synthase (glmS) [18], Neurospora Varkud satellite (VS) [23], twister [8], twister sister [9], pistol [9,10], and hatchet [9,11] These ribozymes are characterised by divergent but similar biochemical properties, with distinctive structures adopting unique catalytic cores. The ribozyme acts as central regulator for gene expression in a negative feedback loop It undergoes a site-specific self-cleavage only upon binding directly to the metabolite glucosamine 6-phosphate.
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