Uncovering Clues to a Natural Gene-Editing Technique

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• Michelle Franklin- [email protected]

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Diversity-generating retroelements (DGRs) are found in the genomes of microorganisms across the globe - from the arctic permafrost to Yellowstone's hot springs and the human gut. DGRs are able to reverse-transcribe RNA back to DNA in a form of natural gene-editing. This process accelerates the evolution of proteins to help microorganisms adapt to changing environments.

Using cryogenic electron microscopy, Partho Ghosh's lab at UC San Diego has figured out the first steps of this accelerated evolution by visualizing the relevant proteins and RNA. They found that RNA especially controlled accelerated evolution, forming structures that started, maintained and stopped the process at the right place. These RNA structures, which were identified in the DGRs of many microorganisms, limited accelerated evolution to proteins needed for adaptation while protecting other essential ones from harm. This research deepens our understanding of the evolutionary origin of DGRs and may be applicable to future gene-editing techniques.

The study was published January 8, 2025 in Nature and was led by Sumit Handa, Tapan Biswas, Jeet Chakraborty, Gourisankar Ghosh, Partho Ghosh (all UC San Diego) and Blair Paul (Marine Biological Laboratory at Woods Hole). Their research was supported by the National Institutes of Health (R01 GM132720, R01 AI163327 and R01 GM033050), the Gordon and Betty Moore Foundation, the G. Unger Vetlesen Foundation, and the Owens Family Foundation.

Read the study in Nature: RNA control of reverse transcription in a diversity-generating retroelement.

DGR RNA (orange and red ribbons) and proteins (dark and light blue surfaces) responsible for the first steps of accelerated protein evolution. The red RNA ribbon is the segment that is reverse-transcribed back to DNA. (cr: Partho Ghosh lab / UC San Diego)