Natural and artificial binders of polyriboadenylic acid and their effect on RNA structure

Abstract

The employment of molecular tools with nucleic acid binding ability to specifically control crucial cellular functions represents an important scientific area at the border between biochemistry and pharmaceutical chemistry. In this review we describe several molecular systems of natural or artificial origin, which are able to bind polyriboadenylic acid (poly(rA)) both in its single-stranded or structured forms. Due to the fundamental role played by the poly(rA) tail in the maturation and stability of mRNA, as well as in the initiation of the translation process, compounds able to bind this RNA tract, influencing the mRNA fate, are of special interest for developing innovative biomedical strategies mainly in the field of anticancer therapy. 1338 Review Polyadenylation in RNA processing Polyadenylation is part of the RNA processing pathway that leads to the production of mature mRNA molecules (Figure 1) [1]. The poly(rA) tail is a long chain of adenine nucleotides that is added to the 3'-end of the primary RNA transcript (pre-mRNA) during the transcription of a specific gene in eukary-otic cells. The pre-mRNA molecule undergoes three main processes (5'-capping, 3'-polyadenylation and RNA splicing) occurring in the cell nucleus before the RNA is exported to the cytoplasm for translation (Figure 1). The pre-mRNA undergoes capping co-transcriptionally as it is released from the RNA

DNA- and RNA-binding ability of oligoDapT, a nucleobase-decorated peptide, for biomedical applications

“…Analogously, we performed a titration experiment also with rA 12 and poly(rA); the latter is an RNA suggested as an important anticancer target. 37,38 The stoichiometry of the obtained oligoDapT/RNA complexes was investigated by adding oligoDapT aliquots to the 1:1 (T Ldap /rA) complex solutions until stabilization of the CD signal: for both rA 12 and poly(rA), the formation of complexes with a 2/1 = T Ldap /rA stoichiometry was evidenced ( Figures 5A and 6A). However, upon titration with the nucleopeptide, To get more insight into the nature of the nucleopeptide/ nucleic acid recognition, and in particular to establish the relative contribution of the electrostatic forces and sequencespecific recognition to the interaction, a binding experiment of oligoDapT with a noncomplementary poly(rU) strand was performed, and the obtained spectra were compared with those shown in Figure 6A for the poly(rA).…”