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.
Highlights
Transcripts are cleaved and polyadenylated at the 3′-end by means of a fine-tuned mechanism mediated by a number of RNA binding proteins and regulatory RNA motifs contained in the 3′ untranslated region (3′-UTR) (Figure 1) [4,5]
Regarding the poly(rA) tail length, it is influenced by the deposition onto mRNAs of nucleophosmin [12], a multifunctional protein able to recognize G-quadruplex-forming nucleic acids [13], whose overexpression is associated with poor prognosis in ovarian cancer [14]
In this review we described several molecular systems, both natural and synthetic, which are able to interact with polyadenylic acid in its single-stranded form or with its ordered forms and complexes
Summary
Polyadenylation is part of the RNA processing pathway that leads to the production of mature mRNA molecules (Figure 1) [1]. Giri and Kumar [32,33] reported that the isoquinoline alkaloid sanguinarine (Figure 3) was able to strongly interact with single-stranded poly(rA) with an association constant of about 4 × 106 M−1 Such binding induced the formation of self-structures in poly(rA) strands and led to cooperative melting transitions, as revealed in circular dichroism, UV and calorimetry studies. Gautier et al [63] studied a new set of synthetic molecules based on an intercalating agent (i.e., oxazolopyridocarbazole (OPC)) covalently bound through a Figure 12: Schematic representation of a L-valine-europium complex This complex was able to induce self-structure in single-stranded poly(rA), and melting experiments led to the conclusion that the observed transition was cooperative similar to the case of a cooperative melting of a DNA double helix. They are able to form adducts with poly(rA), as demonstrated in the study of Lin et al [69] in which a covalent linkage between poly(rA) and dichloroacetonitrile was evidenced
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