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The reaction of soluble RNA with formaldehyde was measured as a function of time. The rate of this reaction can be treated as a combination of simple first‐order rates, such as those observed for the reaction of mononucleotides with formaldehyde. The equilibrium position of the reaction of formaldehyde with soluble RNA in the absence of Mg ++ is consistent with the equilibrium constants observed for mononucleotides. There is no evidence for the occurrence of crosslinking under the conditions used. All the nucleotides of sRNA are available for reaction with formaldehyde in the absence of Mg ++ , even though a considerable amount of secondary structure remains under these conditions. The presence of Mg ++ stabilizes the secondary structure considerably, protecting about two‐thirds of the nucleotides from reaction. The rate of reaction of formaldehyde with sRNA is six times slower than that for mononucleotides. This slowing down of the reaction is interpreted as being due to the weak involvement of the reactive groups in secondary structure, while strong involvement in secondary structure, as in the presence of Mg ++ , prevents reaction completely.
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Penniston et al. (1963) studied this question.
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