Journal
BIOPHYSICAL JOURNAL
Volume 117, Issue 9, Pages 1615-1625Publisher
CELL PRESS
DOI: 10.1016/j.bpj.2019.09.019
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Funding
- Agence Nationale de la Recherche [Dynamic-12-BSV5-0018-02]
- Region Hauts de France'' (Contrat Plan Etat Region Photonics4 Society)
- Region Hauts de France'' (I-PRIMER)
- EquipEX ImaginEx BioMed (Programme d'Investissements d'Avenir/Region Hauts de France)
- Ministerial Funding
- CNRS
- contract Nikon-CNRS
- Singapore Ministry of Education [MOE2016-T2-2-121]
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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.
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