Ribozyme polymerization

Figure 10.13 Phosphoryl-transfer reactions. The figure shows (a) nucleotide polymerization, (b) nucleic acid hydrolysis, (c) first cleavage of an exon-intron junction by group I ribozyme (d) and by a group II ribozyme, (e) strand transfer during transposition and (f) exon ligation during RNA splicing. (From Yang et al., 2006. Copyright 2006, with permission from Elsevier.)...

Fig. 6. A Secondary structure of the class I ligase. B Template-directed RNA polymerization of up to six nucleotides catalyzed by the class I ligase (Ribozyme)...

So far, we have constructed an unsatisfying picture of the earliest days of an RNA world although some prebiotic mechanisms may exist for the untemplated formation of oligonucleotides, these molecules would have been short, would have contained a variety of monomers besides ribotides, and could not have been faithfully copied by the template-directed polymerization of monomers. Given this model, it is difficult to imagine the accumulation of RNA sequences necessary for the Darwinian selection of a multitude of active ribozymes. Nevertheless, these precursors may have been adequate for the first critical step in the formation of life the formation of an RNA replicase. 

Nucleoside-2, 3 -cyclic phosphates have been mentioned as candidates for activated monomers in the context of non-enzymatic polymerizations, and also deserve mention in the context of ribozyme-catalyzed polymerizations. The initial experimental verification of the possibility of a cyclic phosphate... 

Khan A, Benboubetra M, Sayyed PZ, Ng KW, Fox S, Beck G, Benter IF, Akhtar S (2004) Sustained polymeric delivery of gene silencing antisense ODNs, siRNA, DNAzymes and ribozymes in vitro and in vivo studies. J Drug Target 12(6) 393-404... 

Butlerov found out that in alkaline medium (calcium hydroxide), formaldehyde HCHO polymerizes to form about 20 different sugars as racemic mixtures, Butlerov 1861. The reaction requires a divalent metal ion. Breslow found a detailed mechanism of reaction that explains the reaction products, (Breslow 1959). He found that glycol-aldehyde is the first product that is subsequently converted into glyceral-dehyde (a triose), di-hydroxy-acetone, and then into various other sugars, tetrose, pentose, and hexose. The formose reaction advances in an autocatalytic way in which the reaction product is itself the catalyst for that reaction with a long induction period. The intermediary steps proceed via aldol and retro-aldol condensations and, in addition, keto-enol tautomerizations. It remains unexplained how the phosphorylation of 3-glyceraldehyde leads to glycral-3-phosphate (Fig. 3.6). Future work should study whether or not ribozymes exist that can carry out this reaction in a stereo-specific way. 

The self-splicing introns and the RNA component of RNase P (which cleaves the 5 end of tRNA precursors) are two examples of ribozymes. These biological catalysts have the properties of true enzymes. They generally promote hydrolytic cleavage and transesterification, using RNA as substrate. Combinations of these reactions can be promoted by the excised group 1 intron of Tetrahymena rRNA, resulting in a type of RNA polymerization reaction. 

The emergence of longer RNA strings could have proceeded not only via polymerization but also through spontaneous rearrangements of RNA sequences that may progress in the absence of any enzymes or ribozymes [351-353] such rearrangements may have dramatically accelerated evolution [57,354]. 

Asides from chain-growth, step-growth, and multi-step growth strategies, sequence-defined polymers may also be prepared using polymerization concepts inspired by biological polymerizations such as replication, transcription, and translation. For instance, sequence-defined templates can be used for monomer sequence regulation in non-natural polymerizations. Alternatively, catalytic molecular machines inspired by biocatalysts such as enzymes and ribozymes have been tested for the synthesis of sequence-controlled polymers. These developments are summarized in this last section of the chapter. 

Evidence supporting this theory first came from Tom Cech and Sidney Altman s groups, which showed that extant RNAs can function as enzymes, termed ribozymes [8, 9]. Both synthetic and naturally-occurring ribozymes have been shown to make (ligate) and break phosphodiester bonds (the polyanionic backbone of nucleic acids) [10-12], and a derivative of the Class I ligase ribozyme [13] can polymerize up to 95 nucleotides on an RNA primer [14], In addition, RNAs can fold into structures that bind to specific targets. Such RNAs are known as aptamers (from the Latin aptus, meaning to fit ). Many people believe that RNA should be able to direct its own replication. 

Ribozyme An RNA molecule with catalytic activity RNA Polymeric nucleic acid with various functions. 

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