UC San Diego Researchers Uncover a Vast New Landscape of RNA Regulation
In a major advance for understanding how our genes are controlled, scientists have identified dozens of previously unknown molecular "switches" that govern a fundamental process in RNA processing.
The Discovery: 56 New Regulators Found
A large-scale screening of nearly 900 human proteins has dramatically expanded the known list of regulators responsible for alternative polyadenylation (APA) —a process affecting over 70% of human genes. The study, published in Molecular Cell on June 26, 2026, pinpointed 63 high-confidence activators of poly(A) site usage. Notably, 56 of these were entirely new to science, with only seven previously linked to the process.
"This screen reveals a hidden layer of regulation that is far more complex than we anticipated," said Gene Yeo, Professor of Cellular and Molecular Medicine at UC San Diego School of Medicine and co-lead author of the study.
How They Did It: A Novel Screening Approach
Led by researchers at UC San Diego and UC Irvine, the team developed a custom reporter system to methodically measure how each of 879 human RNA-binding proteins influences APA.
- The Surprising Players: Two of the newly identified proteins—GRB2 and RNPS1—were particularly unexpected, as they were found to directly interact with the core APA machinery.
- Predictive Power: The team trained a protein language model that can now predict APA regulators directly from protein sequences, a powerful tool that was validated on an independent set of proteins.
- A New Tool for Control: The study also yielded a programmable, RNA-targeting platform that can recruit specific proteins to individual poly(A) sites, providing a powerful new method for manipulating RNA processing in the lab.
Why This Matters: Implications for Disease
APA is not just a biological curiosity; its misregulation is strongly implicated in cancer, neurological disorders, and other diseases. By mapping these new regulators, the study provides a vital roadmap for future research.
These findings may offer new targets for therapeutic intervention, allowing scientists to potentially correct faulty RNA processing in diseased cells. The research was co-led by Youngsheng Shi, Professor of Microbiology and Molecular Genetics at UC Irvine, alongside Professor Yeo.