Researchers have identified 63 high-confidence activators of poly(A) site usage, a critical process in gene expression. Led by Gene Yeo of UC San Diego and Yongsheng Shi of UC Irvine, the study, published June 26, 2026, in Molecular Cell, provides a new programmable framework for manipulating RNA processing in human cells.
How do these newly discovered proteins influence gene expression?
The research team screened 879 human RNA-binding proteins to determine their role in APA, the process by which a cell selects the “end point” of an RNA molecule. According to the study, 63 proteins were identified as high-confidence activators of poly(A) site usage. Excluding known positive controls, only seven of these proteins had previously been associated with APA. By identifying these regulators, scientists can better understand how cells fine-tune the production of specific proteins.
Alternative polyadenylation (APA) involves poly(A) site usage, the most important step of the APA process.
What is the significance of the protein language model?
To predict APA regulators directly from protein sequences, the researchers developed a protein language model. As reported by the University of California – San Diego, this model successfully identified activators in an independent validation set and highlighted regions of proteins that appear critical for their function. This approach could help accelerate the discovery of RNA regulatory proteins.
Can scientists now control RNA processing?
Beyond identifying new regulators, the team developed a programmable RNA-targeting platform that can recruit proteins to specific poly(A) sites, offering a potential framework for scientists to manipulate RNA processing in a targeted manner. The study specifically highlighted the roles of GRB2 and RNPS1, two proteins not previously known to be associated with APA, which were shown to interact directly with components of the cellular machinery responsible for APA.
How does this study compare to previous RNA research?
This study utilized a large-scale tethered screen to test 879 human RNA-binding proteins. This Molecular Cell publication provides a catalog of regulators that can be used to influence gene expression.
Keep an eye on the development of programmable RNA-targeting platforms.
Frequently Asked Questions
What is alternative polyadenylation (APA)?
APA is a process involving poly(A) site usage.
Why are GRB2 and RNPS1 important?
These proteins were identified as regulators of APA, and neither was known to be associated with APA previously. Their ability to interact with components of the cellular machinery suggests they play a role in APA.
How was the protein language model used?
It was used to predict APA regulators directly from protein sequences, identifying activators in an independent validation set.
Stay updated on the latest breakthroughs in molecular medicine by subscribing to our newsletter or exploring our archive of biotechnology research updates. Have questions about how RNA regulation impacts human health? Drop a comment below.
