Mg²⁺ binding and archaeosine modification stabilize the G15–C48 Levitt base pair in tRNAs

Abstract

The G15–C48 Levitt base pair, located at a crucial position in the core of canonical tRNAs, assumes a reverse Watson–Crick (RWC) geometry. By means of bioinformatics analysis and quantum mechanics calculations we show here that such a geometry is moderately more stable than an alternative bifurcated trans geometry, involving the guanine Watson–Crick face and the cytosine keto group, which we have also found in known RNA structures. However we also demonstrate that the RWC geometry can take advantage of additional stabilizing effects such as metal binding or post-transcriptional chemical modification. One of the few strong metal binding sites characterized for cytosolic tRNAs is localized on G15, and a domain-specific complex modification known as archaeosine is widespread at position 15 in archaeal tRNAs. We have found that both the bound Mg²⁺ ion and the archaeosine modification induce an analogous electron density redistribution, which results in an effective stabilization of the RWC geometry. Metal binding and chemical modification thus play an interchangeable role in stabilizing the G15–C48 correct geometry. Interestingly, these different but convergent strategies are selectively adopted in the different life domains.

Keywords

• tRNA
• tertiary interactions
• metal binding
• post-transcriptional modification
• archaeosine