Anna Ploner,Christoph Mitteregger,Heidelinde Glasner,Raphael Bereiter,Ronald Micura,Kathrin Breuker
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The intrinsic preference of guanosine bases for cleavage-facilitating interactions with phosphodiester moieties in RNA anions revealed by base modifications and mass spectrometry.
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.
期刊介绍:
Nucleic Acids Research (NAR) is a scientific journal that publishes research on various aspects of nucleic acids and proteins involved in nucleic acid metabolism and interactions. It covers areas such as chemistry and synthetic biology, computational biology, gene regulation, chromatin and epigenetics, genome integrity, repair and replication, genomics, molecular biology, nucleic acid enzymes, RNA, and structural biology. The journal also includes a Survey and Summary section for brief reviews. Additionally, each year, the first issue is dedicated to biological databases, and an issue in July focuses on web-based software resources for the biological community. Nucleic Acids Research is indexed by several services including Abstracts on Hygiene and Communicable Diseases, Animal Breeding Abstracts, Agricultural Engineering Abstracts, Agbiotech News and Information, BIOSIS Previews, CAB Abstracts, and EMBASE.