Binding of Al(iii) to synthetic RNA and metal-mediated strand aggregation

Abstract

Over the last few years, focused interest in aluminum has been heightened by recent studies regarding its health effects. Its possible relation with chronic diseases makes it convenient to address more in depth the reactivity of aluminum with biologically relevant molecules. The present work investigates the interaction of the aluminum ion with two synthetic RNAs, poly(rA) and poly(rU), through a detailed thermodynamic and kinetic study. The trivalent aluminum ion was kept in solution by complexation with the cacodylate anion, even at neutral pH, thus making the study with biological molecules feasible. The results obtained by spectrophotometry, circular dichroism, viscometry and thermal stability measurements indicate that aluminium strongly interacts with single and duplex RNA structures. The kinetic experiments point out that, even though cacodylate is required to keep the metal in solution, it actually inhibits the reaction of aluminum with RNA as it converts the metal into an unreactive dimer species. Notably, further interaction occurred in an excess of the aluminum/cacodylate complex, inducing aggregation of single-stranded RNAs. An analysis of the kinetic data has shown that the modes of aggregation of the two RNAs differ and such a difference can be ascribed to the diverse polynucleotide secondary structures. The observed stabilization of multiple-stranded systems by aluminum can serve as a model for future studies due to the interest aroused by this metal in the study of non-canonical nucleic acid structures.

EBER in situ hybridization in subcutaneous aluminum granulomas/lymphoid hyperplasia: A diagnostic clue to differentiate injection‐associated lymphoid hyperplasia from other forms of pseudolymphomas and cutaneous lymphomas

“…The exact mechanism of how the visualization of aluminum by EBER in situ hybridization works within the tissue is up to now unknown. The work of Lari et al 28 investigated the interaction of the aluminum ion with two different synthetic RNAs, poly(rA) and poly(rU), through a detailed thermodynamic and kinetic study. As both free ribonucleotides and polymerized single‐stranded RNA chains, ribonucleotides are highly charged with phosphate, and this system is extremely vulnerable to disruption by a large number of electrostatic forces, and primarily by cationic metals such as aluminum.…”

“…However, the interaction with phosphate seems to prevail in the case of double‐stranded [poly(rA)]. The results of Lari et al indicate that aluminum strongly interacts with single and duplex RNA structures 28 and, thus, explains why EBER in situ hybridization (and assumable any other RNA in situ hybridization method) by the above‐mentioned mechanisms produces (false) positive staining results (Figure 3). Of note, the pattern is not nuclear—as would be awaited from specific detection of EBV‐RNA components—but show a cytoplasmic hue of aluminum‐loaded histiocytes corresponding to the granular cytoplasm on hematoxylin‐eosin staining.…”

Effects of Aluminium Contamination on the Nervous System of Freshwater Aquatic Vertebrates: A Review

“…Additionally, chromatin and DNA are particularly vulnerable to Al 3+ [ 87 ]. Al ions strongly bind DNA, RNA, and mononucleotides [ 12 , 88 , 89 ]. In L. macrochirus, R. rutilus, C. carassius , and N. fluviatilis , exposure to AlCl 3 induced an overexpression of glial fibrillary acidic protein (GFAP), a subunit of the cytoskeleton intermediate filaments, and S100β, a calcium-binding protein mainly present in astrocytes [ 62 , 90 ].…”