High-Fidelity RNA Copying via 2',3'-Cyclic Phosphate Ligation.
J Am Chem Soc
; 146(13): 8887-8894, 2024 Apr 03.
Article
em En
| MEDLINE
| ID: mdl-38503430
ABSTRACT
Templated ligation offers an efficient approach to replicate long strands in an RNA world. The 2',3'-cyclic phosphate (>P) is a prebiotically available activation that also forms during RNA hydrolysis. Using gel electrophoresis and high-performance liquid chromatography, we found that the templated ligation of RNA with >P proceeds in simple low-salt aqueous solutions with 1 mM MgCl2 under alkaline pH ranging from 9 to 11 and temperatures from -20 to 25 °C. No additional catalysts were required. In contrast to previous reports, we found an increase in the number of canonical linkages to 50%. The reaction proceeds in a sequence-specific manner, with an experimentally determined ligation fidelity of 82% at the 3' end and 91% at the 5' end of the ligation site. With splinted oligomers, five ligations created a 96-mer strand, demonstrating a pathway for the ribozyme assembly. Due to the low salt requirements, the ligation conditions will be compatible with strand separation. Templated ligation mediated by 2',3'-cyclic phosphate in alkaline conditions therefore offers a performant replication and elongation reaction for RNA on early Earth.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA
/
RNA Catalítico
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article