The intrinsic preference of guanosine bases for cleavage-facilitating interactions with phosphodiester moieties in RNA anions revealed by base modifications and mass spectrometry
Year: 2025
Type: article
Abstract: Spontaneous backbone cleavage of ribonucleic acids (RNAs) in basic aqueous solution has a preference for the 5' side of guanosine. This phenomenon can also be observed in fully desolvated RNA (M - nH)n- ions subjected to vibrational activation by low-energy collisionally activated dissociation. However, the underlying chemical mechanism of the cleavage reaction has so far remained elusive. Using RNA with site-specific deaza (c1G, c3G, c7G) or methyl (m2G, m22G) modifications and RNA with guanosine to inosine substitution in a comparative study, we show here that preferential cleavage is due to bidentate interactions of guanosine bases with the nonbridging oxygens of phosphodiester moieties on their 5' side. The unimolecular chemistry involved in the RNA cleavage reaction on the 5' side of guanosine may help to understand the evolution of catalytic strategies employed by self-cleaving ribozymes.
Source: Nucleic Acids Research
DOI: 10.1093/nar/gkaf494
Authors: Anna Ploner, Christoph Mitteregger, Heidelinde Glasner, Raphael Bereiter, Ronald Micura, Kathrin Breuker
Institution: Universität Innsbruck
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,992
OpenAlex ID: W4411329212