All known life on Earth relies on the same four-letter genetic alphabet. 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 finding suggests that cells can use their existing molecular machinery to handle synthetic genetic information. That marks an important step toward a long-standing goal in synthetic biology: expanding the language of DNA beyond the four letters found in nature. In the future, such systems could help scientists engineer biological machinery that carries out new functions or produces compounds that do not naturally exist.
How Cells Read an Eight-Letter Genetic Alphabet
The researchers 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, the team 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.
