UC San Diego scientists prove RNA polymerase can read an eight-letter DNA code
UC San Diego researchers demonstrated that a key cellular enzyme can accurately transcribe DNA with an eight-letter alphabet, doubling the natural four letters.
A research group at the University of California, San Diego's Skaggs School of Pharmacy and Pharmaceutical Sciences has provided structural proof that E. coli RNA polymerase can faithfully transcribe DNA containing an eight-letter alphabet. By combining biochemical experiments with sub-atomic cryo-electron microscopy, they captured the enzyme recognizing and inserting two synthetic base pairs, observing that the same biochemical cues guide the reading of both natural and artificial nucleotides.
A companion study in PNAS showed the enzyme also works with a hydrophobic unnatural pair that lacks hydrogen bonding. These findings indicate that existing cellular enzymes can accommodate expanded genetic systems, opening possibilities for new diagnostic tools, therapeutics, and engineered biological pathways. The Nature Communications paper appeared on Sept. 2, 2026, and the PNAS article on Aug. 12, 2026.
Why it matters
It shows that living cells could be reprogrammed to use synthetic DNA, enabling new biotechnologies and therapies.
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