Publications by authors named "Benjamin D Heuberger"

The nonenzymatic replication of RNA oligonucleotides is thought to have played a key role in the origin of life prior to the evolution of ribozyme-catalyzed RNA replication. Although the copying of oligo-C templates by 2-methylimidazole-activated G monomers can be quite efficient, the copying of mixed sequence templates, especially those containing A and U, is particularly slow and error-prone. The greater thermodynamic stability of the 2-thio-U(s(2)U):A base pair, relative to the canonical U:A base pair, suggests that replacing U with s(2)U might enhance the rate and fidelity of the nonenzymatic copying of RNA templates.

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Article Synopsis
  • Structural studies of modified nucleobases, particularly 2-thio-uridine (s(2)U), are essential for understanding RNA stability and pairing specificity.
  • Findings indicate that s(2)U stabilizes U:A base pairs while destabilizing U:G wobble pairs, yet no high-resolution structures of s(2)U-containing RNA duplexes have been previously reported.
  • The authors present two high-resolution structures showing that replacing oxygen with sulfur in s(2)U enhances the stability of U:A pairs without altering the structure, while s(2)U:U pairs are stabilized through a specific pairing conformation due to a unique sulfur-mediated hydrogen bond.
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Two Watson-Crick-like metallo base-pairs are described with mutually independent geometries that have similar dimensions and stabilities to their natural, hydrogen-bonded counterparts.

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Cytosine TNA promotes nonenzymatic, template-directed oligomerization of complementary activated rGMP, leading to selective and efficient formation of RNA products. This process models "genetic takeover" of a pre-RNA by RNA. [reaction: see text]

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