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Scientists Create DNA with Eight Letters Instead of Four

Mayur Tembhare
  1. Researchers at UC San Diego created a new type of DNA that uses eight letters instead of four.

  2. The team focused on RNA polymerase, an enzyme that reads DNA and produces RNA.

  3. Cryo-electron microscopy was used to capture detailed structural views of the enzyme.

  4. The researchers found that RNA polymerase can accurately copy information written using an expanded genetic alphabet.

Scientists Create DNA with Eight Letters Instead of Four

Topic: Biology

Researchers at UC San Diego created a new type of DNA that uses eight letters instead of four. This breakthrough could lead to new technologies and treatments for diseases.

All known life on Earth relies on the same four-letter genetic alphabet. But what if we could use more? Researchers at the University of California San Diego have now shown that one of biology's most important enzymes can accurately read and transcribe a much larger version containing eight genetic letters.

The team focused on RNA polymerase, the enzyme that reads DNA and produces RNA -- the first step in gene expression. To see how the enzyme handles synthetic genetic information, they combined biochemical experiments with high-resolution cryo-electron microscopy capable of revealing structures at scales smaller than the width of a single atom.

The researchers captured detailed structural views of RNA polymerase from Escherichia coli (E. coli) bacteria as it recognized and incorporated two synthetic base pairs. These artificial genetic letters are not found in nature. 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. The potential applications extend well beyond understanding how DNA works. Earlier research has already used expanded genetic alphabets to create synthetic DNA molecules capable of recognizing liver cancer cells.

Why It Matters

This breakthrough could lead to new technologies and treatments for diseases, making it a significant discovery in the field of medicine.

Key Facts

  • Researchers at UC San Diego created a new type of DNA that uses eight letters instead of four.
  • The team focused on RNA polymerase, an enzyme that reads DNA and produces RNA.
  • Cryo-electron microscopy was used to capture detailed structural views of the enzyme.
  • The researchers found that RNA polymerase can accurately copy information written using an expanded genetic alphabet.
  • This breakthrough could lead to new technologies and treatments for diseases.

Key Terms

RNA polymerase
An enzyme that reads DNA and produces RNA, the first step in gene expression
Cryo-electron microscopy
A technique used to capture detailed structural views of molecules at scales smaller than the width of a single atom

Implications

This breakthrough could lead to new technologies and treatments for diseases, making it a significant discovery in the field of medicine.

Source: https://www.sciencedaily.com/releases/2026/09/260904000310.htm

Journal reference:

  1. Qingrong Li, Hyo-Joong Kim, Yan Liu, Juntaek Oh, Peini Hou, Shuichi Hoshika, Grigore Pintilie, Sriram Aiyer, Jenny Chong, Dmitry Lyumkis, Steven A. Benner, Dong Wang. Structural basis of transcription of the hachimoji eight-letter alphabet by E. coli RNA polymerase. Nature Communications, 2026; 17 (1) DOI: 10.1038/s41467-026-76668-0
  2. Qingrong Li, Peini Hou, Michiko Kimoto, Juntaek Oh, Yan Liu, Hui Pen Tan, Jenny Chong, Ichiro Hirao, Dong Wang. Hydrophobic unnatural base pair promotes trigger loop closure and catalysis in cellular RNA polymerase independent of hydrogen bonding. Proceedings of the National Academy of Sciences, 2026; 123 (33) DOI: 10.1073/pnas.2607774123

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