Periodic Reporting for period 1 - LARP4MOT (Structural and functional studies of LARP4, a new RNA binding protein involved in mRNA stabilisation and cell migration)
Reporting period: 2016-09-01 to 2018-08-31
The large number of experiments conducted has significantly furthered our understanding of how LARP4 binds its RNA partner. We revealed unexpected findings (listed below) that, given the high-profile novelty, focused the project more towards molecular recognition and less on cellular biology. A manuscript reported on this work is about to be submitted to a high impact journal.
The main achievements are:
• We have unveiled a completely novel way by which LARP4 recognises its RNA partner, using flexible regions that do not map to any previously identify RNA binding motif (Images 1 and 2).
• The RNA interaction site of LARP4 is a combination of secondary structure elements and disordered regions, which constitutes a breakthrough for the field of RNA-binding proteins and RNA metabolism.
• The La-module structure revealed that it is formed by two independently folded globular domains, the LaM and the RRM1, connected by a short linker (Image1). Although it was initially anticipated to be the main region for RNA binding, unexpectedly was found to play a minor role (Image 2).
• We have revealed an interesting and important interplay between protein-RNA and protein-protein interaction, in that LARP4 binding to oligoA is mutually exclusive with PABP (poly-A binding protein, another RNA binding protein central to life of cell and organisms).
The work performed in the framework of this project is primarily fundamental research, and the biggest impact of the results will be on influencing the research direction of other scientists in academia, biotech and industry working on human diseases that affect a large percentage of the EU population and involve cell migration, cancer, chronic inflammation and heart disease.