Summary information and primary citation
- PDB-id
-
8tdz;
DSSR-derived features in text and
JSON formats
- Class
- RNA
- Method
- X-ray (1.64 Å)
- Summary
- 16mer self-complementary duplex RNA with d:u pair
sequence 2
- Reference
-
Jia X, Fang Z, Kim SC, Ding D, Zhou L, Szostak JW (2024):
"Diaminopurine
in Nonenzymatic RNA Template Copying."
J.Am.Chem.Soc., 146,
15897-15907. doi: 10.1021/jacs.4c02560.
- 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.
