UC San Diego scientists show RNA polymerase reads eight-letter DNA

September 5, 2026 at 10:32 AM2 min

This digest was compiled by AI from multiple sources — links to the originals are below.

Researchers at UC San Diego demonstrated that RNA polymerase from E. coli accurately reads and transcribes synthetic DNA with eight genetic letters. The enzyme recognized two non-natural base pairs using the same structural signals as natural DNA. The findings, published Sept. 2, 2026 in Nature Communications, advance synthetic biology toward expanded genetic codes.

Key Facts

RNA polymerase from E. coli accurately reads and transcribes DNA containing eight genetic letters, including two synthetic base pairs not found in nature.
The study was published on Sept. 2, 2026 in Nature Communications and was led by Dong Wang, PhD, professor at the UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences.
A related study published in PNAS found that RNA polymerase also recognizes another pair of synthetic base pairs that lack hydrogen bonds.
Earlier research used expanded genetic alphabets to create synthetic DNA molecules capable of recognizing liver cancer cells.

Enzyme Recognition Mechanism

The researchers combined biochemical experiments with high-resolution cryo-electron microscopy to capture structural views of RNA polymerase from Escherichia coli as it recognized two synthetic base pairs. The images showed that RNA polymerase identifies the synthetic DNA letters using many of the same biochemical and structural signals it relies on to recognize natural base pairs. This finding helps explain why the enzyme can accurately copy information written using an expanded genetic alphabet. In a related PNAS study, the same team found that RNA polymerase can recognize another pair of synthetic base pairs even though they lack the hydrogen bonds that normally help hold DNA base pairs together.

Potential Applications

Earlier research has already used expanded genetic alphabets to create synthetic DNA molecules capable of recognizing liver cancer cells. The new research provides an important foundation for technologies built around expanded genetic codes by showing in molecular detail how RNA polymerase reads and transcribes non-natural DNA letters. Possible applications include new diagnostic tools, therapeutics, and engineered biological systems with capabilities that do not occur naturally.