Role of tautomerism in RNA biochemistry

Abstract

Heterocyclic nucleic acid bases and their analogs can adopt multiple tautomeric forms due to the presence of multiple solventexchangeable protons. In DNA, spontaneous formation of minor tautomers has been speculated to contribute to mutagenic mispairings during DNA replication, whereas in RNA, minor tautomeric forms have been proposed to enhance the structural and functional diversity of RNA enzymes and aptamers. This review summarizes the role of tautomerism in RNA biochemistry, specifically focusing on the role of tautomerism in catalysis of small self-cleaving ribozymes and recognition of ligand analogs by riboswitches. Considering that the presence of multiple tautomers of nucleic acid bases is a rare occurrence, and that tautomers typically interconvert on a fast time scale, methods for studying rapid tautomerism in the context of nucleic acids under biologically relevant aqueous conditions are also discussed.

Dynamic basis for dG•dT misincorporation via tautomerization and ionization

“…Decades later, it is well established that the replicative and translational machineries form a tight grip around the WC geometry to discriminate against mismatches 2–5 . There is also evidence that both tautomeric 6–13 (Fig. 1b) and anionic 7–9,14,15 (Fig.…”

Watson–Crick-like pairs in CCUG repeats: evidence for tautomeric shifts or protonation

“…3C, D). Minor tautomeric forms are rarely observed but they could be stabilized under favorable conditions (Singh et al 2015) and captured in a crystal structure. It has been proposed that tautomerization in DNA contributes to mutations during polymerization (Wang et al 2011).…”

“…It has been proposed that tautomerization in DNA contributes to mutations during polymerization (Wang et al 2011). In RNA, tautomerization has been postulated to play a role in ribozymes (Singh et al 2015) and in proofreading tRNA during translation (Weixlbaumer et al 2007;Westhof 2014).…”

“…They form slippery duplexes in which the noncanonical base pairs are apparently stabilized by a shift to uncommon tautomeric or ionic forms. The possibility of tautomeric transitions of the common nucleobases has long been recognized but only recently has their role in biological processes been demonstrated (Demeshkina et al 2012(Demeshkina et al , 2013Singh et al 2015). Tautomeric and anionic forms of the bases are believed to contribute to DNA mutagenesis, errors during translation, nucleic acid catalysis, and RNA-ligand recognition (Bevilacqua and Yajima 2006;Weixlbaumer et al 2007;Gilbert et al 2009;Wang et al 2011).…”

A Polymerase Tautomeric Model for Radiation Induced Bystander Effects: A Model for Untargeted Base Substitution Mutagenesis during Error Prone and SOS Replication of Double Stranded DNA Containing Thymine and Adenine in Rare Tautomeric Forms

“…For DNA polymerase V, having the lowest rate of synthesis it is not more than 0.1 seconds. Since the time required for bases came into contact with the water molecule and has changed they tautomeric state, more than 0.1 seconds, we see that the probability of such a process is quite small [84].The results of studies on the structure of the active centers of polymerases show that the bases in rare tautomeric forms may exist in the active centers of polymerases [130][131][132][133][134][135]. More details on this issue is set out in ref [98].…”