HEXIM1 Diffusion in the Nucleus Is Regulated by Its Interactions with Both 7SK and P-TEFb

Alessandro Furlan (1) , Mariano Gonzalez-Pisfil (1) , Aymeric Leray (2) , Dorian Champelovier (1) , Mélanie Henry (1) , Corentin Le Nézet (1) , Oliver Bensaude , Marc Lefranc (1) , Thorsten Wohland , Bernard Vandenbunder , Gabriel Bidaux (3) , Laurent Héliot (1)

1 PhLAM - Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523
2 ICB - Laboratoire Interdisciplinaire Carnot de Bourgogne
3 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition

How nuclear proteins diffuse and find their targets remains a key question in the transcription field. Dynamic proteins in the nucleus are classically subdiffusive and undergo anomalous diffusion, yet the underlying physical mechanisms are still debated. In this study, we explore the contribution of interactions to the generation of anomalous diffusion by the means of fluorescence spectroscopy and simulation. Using interaction-deficient mutants, our study indicates that HEXIM1 interactions with both 7SK RNA and positive transcription elongation factor b are critical for HEXIM1 subdiffusion and thus provides evidence of the effects of protein-RNA interaction on molecular diffusion. Numerical simulations allowed us to establish that the proportions of distinct oligomeric HEXIM1 subpopulations define the apparent anomaly parameter of the whole population. Slight changes in the proportions of these oligomers can lead to significant shifts in the diffusive features and recapitulate the modifications observed in cells with the various interaction-deficient mutants. By combining simulations and experiments, our work opens new prospects in which the anomaly a coefficient in diffusion becomes a helpful tool to infer alterations in molecular interactions.

Domaines: Sciences du Vivant [q-bio]

Alessandro Furlan, Mariano Gonzalez-Pisfil, Aymeric Leray, Dorian Champelovier, Mélanie Henry, et al.. HEXIM1 Diffusion in the Nucleus Is Regulated by Its Interactions with Both 7SK and P-TEFb. Biophysical Journal, 2019, 117 (9), pp.1615-1625. ⟨10.1016/j.bpj.2019.09.019⟩. ⟨hal-03060372⟩