Sequence-specific cleavage of oligoribonucleotide capable of forming a stem and loop structure.

Hosaka, Hideo; Sakabe, Ichiro; Sakamoto, Kensaku; Yokoyama, S; Takaku, Hiroshi

doi:10.1016/s0021-9258(17)32131-2

Cited by 19 publications

(4 citation statements)

References 40 publications

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“…The hydrolytic stability of RNA phosphodiester bonds strongly depends on the molecular environment. [62] While the influence of base moiety structure on cleavage or isomerization of dinucleoside-3',5'-monophosphates is under physiological conditions rather modest, [31] studies with natural RNA oligomers [63][64][65][66] and synthetic oligonucleotides [67][68][69] have shown that 3',5'-UpA, 3',5'-UpG, 3',5'-CpA and 3',5'-CpG linkages often are exceptionally labile. In other words, a combination of 3'-linked pyrimidine and 5'-purine nucleoside constitutes a favourable cleavage site.…”

Section: Studies With Oligoribonucleotidesmentioning

confidence: 99%

Structural Modifications as Tools in Mechanistic Studies of the Cleavage of RNA Phosphodiester Linkages

Lönnberg

2022

The Chemical Record

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The cleavage of RNA phosphodiester bonds by RNase A and hammerhead ribozyme at neutral pH fundamentally differs from the spontaneous reactions of these bonds under the same conditions. While the predominant spontaneous reaction is isomerization of the 3',5'phosphodiester linkages to their 2',5'-counterparts, this reaction has never been reported to compete with the enzymatic cleavage reaction, not even as a minor side reaction. Comparative kinetic measurements with structurally modified di-nucleoside monophosphates and oligomeric phosphodiesters have played an important role in clarification of mechanistic details of the buffer-independent and buffer-catalyzed reactions. More recently, heavy atom isotope effects and theoretical calculations have refined the picture. The primary aim of all these studies has been to form a solid basis for mechanistic analyses of the action of more complicated catalytic machineries. In other words, to contribute to conception of a plausible unified picture of RNA cleavage by biocatalysts, such as RNAse A, hammerhead ribozyme and DNAzymes. In addition, structurally modified trinucleoside monophosphates as transition state models for Group I and II introns have clarified some features of the action of large ribozymes.

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Section: Studies With Oligoribonucleotidesmentioning

confidence: 99%

Structural Modifications as Tools in Mechanistic Studies of the Cleavage of RNA Phosphodiester Linkages

Lönnberg

2022

The Chemical Record

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“…The base composition is known to have only a modest effect on the alkaline cleavage of the phosphodiester bond of dinucleoside monophosphates (12,15,16) and diphosphates (17) or short chimeric DNA-RNA oligonucleotides (14): up to 5-fold differences have been reported. In the context of natural RNA polymers, 5′-UpA-3′ and 5′-CpA-3′ phosphodiester bonds have frequently been observed as less stable than those flanked by other nucleosides (18)(19)(20)(21)(22). Efficient and selective cleavage of the 5′-UpA-3′ bond within synthetic oligoribonucleotides in the presence of organic cofactors, such as polyvinylpyrrole, has been extensively documented (23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

The reactivity of phosphodiester bonds within linear single-stranded oligoribonucleotides is strongly dependent on the base sequence

Kaukinen

Lyytikäinen

Mikkola

et al. 2002

Nucleic Acids Research

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The cleavage of short chimeric oligonucleotides containing only one reactive ribonucleoside unit, all other nucleosides being 2'-O-methylated, has been studied at pH 8.5 and 35 degrees C. Among the 20 different sequences that did not exhibit any tendency to form a defined secondary structure, the scissile 5'-UpA-3' and 5'-CpA-3' phosphodiester bonds experienced >100- and up to 35-fold reactivity differences, respectively. Compared with dinucleoside monophosphates, both rate accelerations and retardations of more than one order of magnitude were observed. Even a change of a single base several nucleosides away from the scissile bond markedly affected the reaction rate. Duplex formation at the 3'- and/or 5'-side of the scissile bond was also studied and observed to be strongly rate retarding. The origin of the high sensitivity of phosphodiester bonds to the molecular environment is discussed.

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“…In particular, the internucleosidic linkages between 5Ј-UpA-3Ј and 5Ј-CpA-3Ј, in the context of natural RNA polymers, have frequently been reported as less stable than those flanked by other nucleosides. [14][15][16][17][18] Efficient and selective cleavage of the 5Ј-UpA-3Ј bond within synthetic oligoribonucleotides in the presence of organic cofactors, has also been documented. [19][20][21] Recent extensive studies with single-stranded oligoribonucleotides, however, show that the reactivity of an individual phosphodiester bond is strongly dependent on the base sequence of the whole oligomer.…”

Section: Introductionmentioning

confidence: 99%

The base sequence dependent flexibility of linear single-stranded oligoribonucleotides correlates with the reactivity of the phosphodiester bond

et al. 2003

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The effect of base sequence on the structure and flexibility of linear single-stranded RNA molecules and the influence of the base sequence on phosphodiester bond reactivity have been studied. Molecular dynamics simulations of 2.1 ns were carried out for nine chimeric oligonucleotides containing only one unsubstituted ribo unit, all the rest of sugars being 2'-O-methylated. The base sequence has recently been reported to make a big contribution to the reactivity of these compounds. A detailed examination of the interaction energies between the base moieties shows that base stacking is strongly context-dependent and cooperative. The strength of stacking at the site susceptible to chain cleavage by intramolecular transesterification was observed to be dependent on both the flanking bases of the cleavage site and those further apart in the molecule. The interaction energies between the bases in the vicinity of the scissile linkage were found to correlate well with the experimental phosphodiester bond cleavage rates: the stronger the bases close to the cleavage site are stacked, the slower the cleavage rate is.

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Sequence-specific cleavage of oligoribonucleotide capable of forming a stem and loop structure.

Cited by 19 publications

References 40 publications

Structural Modifications as Tools in Mechanistic Studies of the Cleavage of RNA Phosphodiester Linkages

Structural Modifications as Tools in Mechanistic Studies of the Cleavage of RNA Phosphodiester Linkages

The reactivity of phosphodiester bonds within linear single-stranded oligoribonucleotides is strongly dependent on the base sequence

The base sequence dependent flexibility of linear single-stranded oligoribonucleotides correlates with the reactivity of the phosphodiester bond

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