Limits...
From formamide to RNA, the path is tenuous but continuous.

Pino S, Sponer JE, Costanzo G, Saladino R, Mauro ED - Life (Basel) (2015)

Bottom Line: Reactions of formamide (NH2COH) in the presence of catalysts of both terrestrial and meteoritic origin yield, in plausible and variegated conditions, a large panel of precursors of (pre)genetic and (pre)metabolic interest.Formamide chemistry potentially satisfies all of the steps from the very initial precursors to RNA.Water chemistry enters the scene in RNA non-enzymatic synthesis and recombination.

View Article: PubMed Central - PubMed

Affiliation: Fondazione "Istituto Pasteur-Fondazione Cenci-Bolognetti" c/o Dipartimento di Biologia e Biotecnologie "Charles Darwin", "Sapienza" Università di Roma, P.le Aldo Moro, 5, 00185 Rome, Italy. samantapino78@libero.it.

ABSTRACT
Reactions of formamide (NH2COH) in the presence of catalysts of both terrestrial and meteoritic origin yield, in plausible and variegated conditions, a large panel of precursors of (pre)genetic and (pre)metabolic interest. Formamide chemistry potentially satisfies all of the steps from the very initial precursors to RNA. Water chemistry enters the scene in RNA non-enzymatic synthesis and recombination.

No MeSH data available.


The ligation following intermolecular cleavage (LIC) mechanism. The reaction between C24 and 5'-phosphorylated G24 is shown as an example. Ligation assuming loop formation at the 3'-end of C24 and attack at the phosphorylated 5'-end of G24 leads to the formation of C24G24. Simultaneous cleavage reaction initiated by the attack of the 3'-end of C24 at the penultimate phosphate of the 5'-phosphorylated G24. The products of this reaction are C24G23 and 5'-phosphorylated guanosine-phosphate, which readily combines with another C24, leading to the formation of C24G (see [34]).
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life-05-00372-f005: The ligation following intermolecular cleavage (LIC) mechanism. The reaction between C24 and 5'-phosphorylated G24 is shown as an example. Ligation assuming loop formation at the 3'-end of C24 and attack at the phosphorylated 5'-end of G24 leads to the formation of C24G24. Simultaneous cleavage reaction initiated by the attack of the 3'-end of C24 at the penultimate phosphate of the 5'-phosphorylated G24. The products of this reaction are C24G23 and 5'-phosphorylated guanosine-phosphate, which readily combines with another C24, leading to the formation of C24G (see [34]).

Mentions: The prebiotically relevant point here is that this reaction occurs by the action of spontaneously-generated polymers derived from abiotically plausible precursors, enhancing the information content of a polymeric mixture. This mechanism potentially represents a plausible means to generate RNA sequence complexity and to approach the questions: how could the extremely complex ribosomal machinery [60] start to evolve, and how did the initial RNA transfer functions [61] come about? The proposed mechanism for the LIC reaction is described in Figure 5 and Figure 6. As observed [34], Watson–Crick-type base-complementarity is needed to achieve self-cleavage of the interacting oligomers. In order to put the ligation and cleavage reactions into a common frame and fulfill the requirements of Watson–Crick complementarity, the two interacting strands are ideally shifted in register by 3–4 bases (Figure 5), enabling the formation of a loop at the 3'-end of the acceptor strand. This loop formation is necessary to bring the 3'-end into an in-line attacking position at the 5'-phosphorylated end of the donor strand (Figure 5). At the same time, the loop can easily adopt also a geometry in which the 5'-phosphorylated end is attacked at the penultimate phosphate group (Figure 5), which becomes accessible to nucleophilic attack due to end-fraying. These considerations suggest that Watson–Crick base pairing combined with the ability to form stable loop geometries could provide the structural basis of the catalytic activity of the first RNA-oligomers. Based on detailed computations of the free energy profiles of the ligation and cleavage reactions, a consistent model for these reactions that lead to terminal RNA recombination has been formulated (Figure 6) [34].


From formamide to RNA, the path is tenuous but continuous.

Pino S, Sponer JE, Costanzo G, Saladino R, Mauro ED - Life (Basel) (2015)

The ligation following intermolecular cleavage (LIC) mechanism. The reaction between C24 and 5'-phosphorylated G24 is shown as an example. Ligation assuming loop formation at the 3'-end of C24 and attack at the phosphorylated 5'-end of G24 leads to the formation of C24G24. Simultaneous cleavage reaction initiated by the attack of the 3'-end of C24 at the penultimate phosphate of the 5'-phosphorylated G24. The products of this reaction are C24G23 and 5'-phosphorylated guanosine-phosphate, which readily combines with another C24, leading to the formation of C24G (see [34]).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390857&req=5

life-05-00372-f005: The ligation following intermolecular cleavage (LIC) mechanism. The reaction between C24 and 5'-phosphorylated G24 is shown as an example. Ligation assuming loop formation at the 3'-end of C24 and attack at the phosphorylated 5'-end of G24 leads to the formation of C24G24. Simultaneous cleavage reaction initiated by the attack of the 3'-end of C24 at the penultimate phosphate of the 5'-phosphorylated G24. The products of this reaction are C24G23 and 5'-phosphorylated guanosine-phosphate, which readily combines with another C24, leading to the formation of C24G (see [34]).
Mentions: The prebiotically relevant point here is that this reaction occurs by the action of spontaneously-generated polymers derived from abiotically plausible precursors, enhancing the information content of a polymeric mixture. This mechanism potentially represents a plausible means to generate RNA sequence complexity and to approach the questions: how could the extremely complex ribosomal machinery [60] start to evolve, and how did the initial RNA transfer functions [61] come about? The proposed mechanism for the LIC reaction is described in Figure 5 and Figure 6. As observed [34], Watson–Crick-type base-complementarity is needed to achieve self-cleavage of the interacting oligomers. In order to put the ligation and cleavage reactions into a common frame and fulfill the requirements of Watson–Crick complementarity, the two interacting strands are ideally shifted in register by 3–4 bases (Figure 5), enabling the formation of a loop at the 3'-end of the acceptor strand. This loop formation is necessary to bring the 3'-end into an in-line attacking position at the 5'-phosphorylated end of the donor strand (Figure 5). At the same time, the loop can easily adopt also a geometry in which the 5'-phosphorylated end is attacked at the penultimate phosphate group (Figure 5), which becomes accessible to nucleophilic attack due to end-fraying. These considerations suggest that Watson–Crick base pairing combined with the ability to form stable loop geometries could provide the structural basis of the catalytic activity of the first RNA-oligomers. Based on detailed computations of the free energy profiles of the ligation and cleavage reactions, a consistent model for these reactions that lead to terminal RNA recombination has been formulated (Figure 6) [34].

Bottom Line: Reactions of formamide (NH2COH) in the presence of catalysts of both terrestrial and meteoritic origin yield, in plausible and variegated conditions, a large panel of precursors of (pre)genetic and (pre)metabolic interest.Formamide chemistry potentially satisfies all of the steps from the very initial precursors to RNA.Water chemistry enters the scene in RNA non-enzymatic synthesis and recombination.

View Article: PubMed Central - PubMed

Affiliation: Fondazione "Istituto Pasteur-Fondazione Cenci-Bolognetti" c/o Dipartimento di Biologia e Biotecnologie "Charles Darwin", "Sapienza" Università di Roma, P.le Aldo Moro, 5, 00185 Rome, Italy. samantapino78@libero.it.

ABSTRACT
Reactions of formamide (NH2COH) in the presence of catalysts of both terrestrial and meteoritic origin yield, in plausible and variegated conditions, a large panel of precursors of (pre)genetic and (pre)metabolic interest. Formamide chemistry potentially satisfies all of the steps from the very initial precursors to RNA. Water chemistry enters the scene in RNA non-enzymatic synthesis and recombination.

No MeSH data available.