A Mechanistic Explanation for the Regioselectivity of Nonenzymatic RNA Primer Extension.
A Mechanistic Explanation for the Regioselectivity of Nonenzymatic RNA Primer Extension.
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DOI：
10.1021/jacs.7b08784
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发表时间：
2017-11-22
影响因子：
15
通讯作者：
Szostak JW
中科院分区：
文献类型：
--
作者：
Giurgiu C;Li L;O'Flaherty DK;Tam CP;Szostak JW
A working model of nonenzymatic RNA primer extension could illuminate how prebiotic chemistry transitioned to biology. All currently known experimental reconstructions of nonenzymatic RNA primer extension yield a mixture of 2′-5′ and 3′-5′ internucleotide linkages. Although long seen as a major problem, the causes of the poor regioselectivity of the reaction are unknown. We used a combination of different leaving groups, nucleobases, and templating sequences to uncover the factors that yield selective formation of 3′-5′ internucleotide linkages. We found that fast and high yielding reactions selectively form 3′-5′ linkages. Additionally, in all cases with high 3′-5′ regioselectivity, Watson–Crick base pairing between the RNA monomers and the template is observed at the extension site and at the adjacent downstream position. Mismatched base-pairs and other factors that would perturb the geometry of the imidazolium bridged intermediate lower both the rate and regioselectivity of the reaction.
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DOI：
10.1073/pnas.1610103113
发表时间：
2016-08-30
影响因子：
11.1
作者：
Horning, David P.;Joyce, Gerald F.
通讯作者：
Joyce, Gerald F.
影响因子：
5.6
作者：
CRICK, FHC
通讯作者：
CRICK, FHC
影响因子：
1.2
作者：
Kozlov, IA;Orgel, LE
通讯作者：
Orgel, LE
影响因子：
56.9
作者：
LOHRMANN, R;BRIDSON, PK;ORGEL, LE
通讯作者：
ORGEL, LE
影响因子：
15
作者：
Rohatgi, R;Bartel, DP;Szostak, JW
通讯作者：
Szostak, JW