Séminaire Département de Biologie - Dr. Arnaud HUBSTENBERGER

Lundi 13 juin 2016 à 11h00 en Amphithéâtre Gregory

Dr Arnaud HUBSTENBERGER, CNRS-UMR7622, Laboratoire de Biologie du Développement
Institut de Biologie Paris-Seine, Université Pierre et Marie Curie

RNP transitions between soluble, liquid and solid phases and the coordination of mRNA expression

While a large number of transcriptomes are now available, the central question remains: how do mRNAs organize on a large scale to coordinate expression? A first layer of control is regulatory proteins binding mRNAs to form ribonucleoproteins (RNP) complexes. Another layer of coordination is the ability of RNPs to condense to compartmentalize thousands of molecules within granules. Using C elegans germline as a model, we previously showed how mRNPs that form cytosolic P-bodies can undergo phase transitions between diffuse, liquid and solid states and identified regulators of such transitions (1,2). These regulated phase transitions coordinate the exchange of RNAs, their local concentrations, and their subcellular distributions during development. Here, we combined imaging, biophysics, genetic screens and an innovative RNP granule purification technique, conducted transcriptomic and proteomic analyses, and demonstrated conserved structure and functions from germline P-bodies in C. elegans to somatic P-bodies in H. sapiens. We dissected the key role of polyQ prion-like peptides, that are part of larger intrinsically disordered regions, in the structural mechanisms of RNP phase transitions. We showed the conserved functionality of mRNA condensation in coordinating and fine tuning the translational repression of specific mRNA regulons. Our work underlies the importance of higher scale RNP super-assemblies in coordinating the fate of a large RNA collective.

1. Hubstenberger, A., Noble, S.L., Cameron, C., and Evans, T.C. (2013). Translation Repressors, an RNA Helicase, and Developmental Cues Control RNP Phase Transitions during Early Development. Dev Cell 27, 161-173.
2. Hubstenberger, A.*, Cameron, C., Noble, S.L., Keenan S., and Evans, T.C (2015). Modifiers of solid RNP granules control normal RNP dynamics and mRNA activity in early development. J Cell Biol 211(3), 703–16.