UC San Diego researchers enable RNA polymerase to read eight-letter DNA alphabet

Researchers at the University of California, San Diego have shown that a fundamental cellular enzyme can accurately read an expanded eight‑letter genetic alphabet, effectively doubling the four nucleobases that comprise the DNA of all known life. Using high‑resolution imaging techniques, the team observed that RNA polymerase—a protein responsible for transcribing DNA into RNA—processes synthetic DNA letters in a manner remarkably similar to its handling of natural nucleotides, confirming that the enzyme can incorporate and interpret the additional bases without loss of fidelity.

The discovery marks a significant step toward the development of synthetic genetic systems capable of encoding novel biological functions beyond those found in nature. By demonstrating that the core transcription machinery tolerates an enlarged alphabet, the research opens pathways for engineering organisms with new properties, such as the production of unconventional proteins or the storage of extra information in living cells.