New fundamental property of the Argonaute proteins discovered
In a new collaborative paper published in Nature Structural & Molecular Biology, researchers are reporting a fundamental new discovery on Argonaute proteins.
Argonaute proteins are molecular machines required for the function of microRNAs whose discovery was the basis for the 2024 Nobel Prize in medicine and physiology.
microRNAs bind to Argonaute proteins thereby programming them to regulate genes with sequence specificity. This type of Argonaute-microRNA-dependent genetic control is key to animal and plant development and physiology, and the RNA-programmable Argonaute system is central to new therapies using microRNA mimics to control the activity of specific genes linked to disease states in humans.
- “We have known for 15 years, that while RNA-bound Argonaute proteins are stable, free Argonaute proteins are rapidly degraded, a key observation without a clear molecular explanation. Our new study identifies a structural switch conserved from plant to human Argonaute proteins that is uniquely accessible in free Argonaute proteins and that directs their rapid degradation,” explains Peter Brodersen, professor at the Department of Biology and last author of the paper.
This discovery opens new areas of investigation on the Argonaute-microRNA system with implications for vastly different biological phenomena, ranging from neurological diseases in humans to antiviral immunity in plants.
The study was carried out by research groups from the Department of Biology, University of Copenhagen, led by Peter Brodersen, Birthe B. Kragelund & Rasmus Hartmann-Petersen and Anders H. Lund from the Biotech Research and Innovation Centre.
Read the paper here: Importance of an N-terminal structural switch in the distinction between small RNA-bound and free ARGONAUTE