8TDZ

16mer self-complementary duplex RNA with D:U pair sequence 2

8TDZ の概要

• エントリーDOI: 10.2210/pdb8tdz/pdb
• 分子名称: RNA, COBALT HEXAMMINE(III) (3 entities in total)
• 機能のキーワード: diaminopurine, rna, non-canonical base pair
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 5259.19

構造登録者

Fang, Z.,Jia, X.,Szostak, J.W. (登録日: 2023-07-05, 公開日: 2024-06-12, 最終更新日: 2024-06-26)

主引用文献

Jia, X.,Fang, Z.,Kim, S.C.,Ding, D.,Zhou, L.,Szostak, J.W.
Diaminopurine in Nonenzymatic RNA Template Copying.
J.Am.Chem.Soc., 146:15897-15907, 2024

PubMed Abstract: In the RNA World before the emergence of an RNA polymerase, nonenzymatic template copying would have been essential for the transmission of genetic information. However, the products of chemical copying with the canonical nucleotides (A, U, C, and G) are heavily biased toward the incorporation of G and C, which form a more stable base pair than A and U. We therefore asked whether replacing adenine (A) with diaminopurine (D) might lead to more efficient and less biased nonenzymatic template copying by making a stronger version of the A:U pair. As expected, primer extension substrates containing D bound to U in the template more tightly than substrates containing A. However, primer extension with D exhibited elevated reaction rates on a C template, leading to concerns about fidelity. Our crystallographic studies revealed the nature of the D:C mismatch by showing that D can form a wobble-type base pair with C. We then asked whether competition with G would decrease the mismatched primer extension. We performed nonenzymatic primer extension with all four activated nucleotides on randomized RNA templates containing all four letters and used deep sequencing to analyze the products. We found that the DUCG genetic system exhibited a more even product distribution and a lower mismatch frequency than the canonical AUCG system. Furthermore, primer extension is greatly reduced following all mismatches, including the D:C mismatch. Our study suggests that D deserves further attention for its possible role in the RNA World and as a potentially useful component of artificial nonenzymatic RNA replication systems.

PubMed: 38818863
DOI: 10.1021/jacs.4c02560

実験手法

X-RAY DIFFRACTION (1.64 Å)