Scientists uncover new role for disordered protein regions in RNA recognition
The findings shed new light on how the RNA-binding protein LARP6 influences diseases such as fibrosis and cancer
Researchers from the University of Oxford and collaborators have identified a previously unknown mechanism by which intrinsically disordered regions (IDRs) in RNA-binding proteins help determine RNA target specificity. The findings, published this week in Nature Communications, shed new light on how the RNA-binding protein LARP6 influences diseases such as fibrosis and cancer.
Faraz Mardakheh
Faraz Mardakheh, Principal Investigator at the Oxford University’s Department of Biochemistry, says: “RNA-binding proteins (RBPs) often contain large stretches of IDRs—regions that lack fixed structure. Although common, the function of these segments in RNA recognition has remained unclear. In the new study, we focused on LARP6, a highly conserved RBP known for its diverse RNA targets and its involvement in cancer progression and fibrosis.”
Using a multidisciplinary approach, the team discovered that IDRs act as “selectivity gates”, regulating how adjacent-structured RNA-binding domains interact with their RNA targets. The IDRs restrict the conformations available to the folded domain, control RNA access, and form additional contacts with the correct RNA sequences. Together, these effects produce a highly selective RNA-binding behaviour.
Importantly, the team demonstrated that this IDR-mediated selectivity is essential for LARP6’s role in promoting cancer cell viability and invasion, highlighting its potential relevance for future therapeutic strategies.
The work was led jointly by the laboratories of Faraz Mardakheh and Sasi Conte, with major contributions from first authors Federica Capraro and Giancarlo Abis. The study involved various researchers from King’s College London, Barts Cancer Institute, University of California San Francisco, and Arc Institute. BBSRC, MRC, and Leverhulme Trust funded this project.
