Non-canonical 3′-5′ Extension of RNA with Prebiotically Plausible Ribonucleoside 2′,3′-Cyclic Phosphates,Journal of the American Chemical Society

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Non-canonical 3′-5′ Extension of RNA with Prebiotically Plausible Ribonucleoside 2′,3′-Cyclic Phosphates
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2014-03-28 , DOI: 10.1021/ja4127714
Hannes Mutschler ₁ , Philipp Holliger

Affiliation

Ribonucleoside 2′,3′-cyclic phosphates (N>p’s) are generated by multiple prebiotically plausible processes and are credible building blocks for the assembly of early RNA oligomers. While N>p’s can be polymerized into short RNAs by non-enzymatic processes with variable efficiency and regioselectivity, no enzymatic route for RNA synthesis had been described. Here we report such a non-canonical 3′-5′ nucleotidyl transferase activity. We engineered a variant of the hairpin ribozyme to catalyze addition of all four N>p’s (2′,3′-cyclic A-, G-, U-, and CMP) to the 5′-hydroxyl termini of RNA strands with 5′ nucleotide addition enhanced in all cases by eutectic ice phase formation at −7 °C. We also observed 5′ addition of 2′,3′-cyclic phosphate-activated β-nicotinamide adenine dinucleotide (NAD>p) and ACA>p RNA trinucleotide, and multiple additions of GUCCA>p RNA pentamers. Our results establish a new mode of RNA 3′-5′ extension with implications for RNA oligomer synthesis from prebiotic nucleotide pools.

中文翻译：

用益生元合理的核糖核苷 2',3'-环状磷酸盐对 RNA 进行非规范 3'-5' 延伸

核糖核苷 2',3'-环状磷酸盐 (N>p's) 由多个益生元合理的过程产生，是早期 RNA 寡聚体组装的可靠构件。虽然 N>p 可以通过具有可变效率和区域选择性的非酶促过程聚合成短 RNA，但尚未描述 RNA 合成的酶促途径。在这里，我们报告了这种非规范的 3'-5' 核苷酸转移酶活性。我们设计了一种发夹核酶的变体，以催化将所有四个 N>p（2'、3'-环状 A-、G-、U- 和 CMP）添加到具有 5' 的 RNA 链的 5'-羟基末端在所有情况下，-7 °C 时共晶冰相的形成都增强了核苷酸的添加。我们还观察到 5' 添加 2',3'-环状磷酸激活的 β-烟酰胺腺嘌呤二核苷酸 (NAD>p) 和 ACA>p RNA 三核苷酸，并多次添加 GUCCA>p RNA 五聚体。我们的结果建立了一种新的 RNA 3'-5' 延伸模式，对从益生元核苷酸库中合成 RNA 寡聚体有影响。

更新日期：2014-03-28

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