October 15, 2026 — Years ago Dr. Joshua Rosenthal and colleagues made a surprising discovery: cephalopods such as squid, octopuses, and cuttlefish, are highly active RNA “recoders”, making thousands of edits to the genetic instructions inside their cells—far more than other animals. Since then, they and others have demonstrated how a selection of these RNA edits alter protein function. Building on this body of work, a new study from the University of California, San Francisco (UCSF) in collaboration with the Rosenthal Lab at the Marine Biology Laboratory (MBL), dramatically increased the scale at which we can measure what these edits do and how they affect the microscopic machines inside squid cells.

Published on October 15 in Cell, the study, “Functional diversification of the cephalopod proteome by RNA-editing”, addresses what happens to edited RNA in cephalopods. Initiated and led by a talented UCSF Postdoctoral Researcher Dr. Jack Moen, with Dr. Danielle Swaney as the corresponding author, this collaboration brought together experts in proteomic and marine biology from both coasts of the continental United States.

In the simplified central dogma of biology, genes are encoded by DNA and transcribed into temporary messages made of RNA, which are translated into functional products called proteins. Special editing enzymes can modify RNA messages before a protein is made, creating a new “recoded” protein product. While identifying edits in RNA is not trivial, identifying recoding events in proteins has been particularly laborious and challenging due in part to the exponential amplification in the “search” space.

Now, with the aid of Tesorai’s AI-assisted search model, researchers have reported nearly 8,000 editing events in more than 2,000 recoded proteins, representing 20% of all the proteins identified in the squid cells, and greatly expanding the known library of edited proteins. Recoded proteins contained sequences that had never before been recorded in any of the more than 14,000 species databases available in public repositories.

“These findings reveal how much biological variety can come from the same genetic starting point,” said Jack Moen, PhD, the first author on the study. “A cell isn’t dependent on just the instructions stored in its DNA, but also on how those instructions are edited. Squids have capitalized on this process to create a never-before-seen biological diversity within their cells.”

Researchers also show that RNA editing produced recoded proteins that have altered thermal stability, solubility, and activity, meaning the fundamental nature of the protein had been altered from its unedited version. In addition, researchers found that many recoded proteins changed their location and interacting partners inside the cell, moving into different cellular compartments and altering organelle functions.

When asked about the future of this research, Dr. Moen said, “We’ve shown that these edits can change how proteins work. The next step is to understand what it means for a living animal. Answering these questions could reveal how these organisms utilize this type of molecular flexibility.”

Image: Doryteuthis pealeii, the longfin inshore squid swimming through the Atlantic waters. Image credit: Roger T. Hanlon, Senior Scientist, The Marine Biological Laboratory.