Intrinsic Disorder and Salt-dependent Conformational Changes of the N-terminal TFIP11 Splicing Factor

editorial reviewedAbstractTuftelin Interacting Protein 11 (TFIP11) was recently identified as a critical human spliceosome assembly regulator. Indeed, it is involved in many biological functions including the interaction with multiple spliceosome key proteins and its localisation in several membrane-less organelles. However, there is a lack of structural information on TFIP11, which limits the rationalisation of its biological role. TFIP11 has been predicted as a highly disordered protein, and specifically concerning its N-terminal (N-TER) region. Intrinsically disordered proteins (IDPs) lack a defined tertiary structure, existing as a dynamic conformational ensemble, which favours their role as hubs in protein-protein and protein-RNA interaction networks. Furthermore, IDPs are involved in liquid-liquid phase separation (LLPS) which drives the formation of subnuclear compartments. In this study, we have refined the disorder prediction of TFIP11 N-TER region and subsequently performed all-atom molecular dynamics (MD) simulations to assess its conformational flexibility and the interplay between their different N-TER domains. We further confirm that TFIP11 may be described as a polyampholyte IDP with a flexible conformation. Furthermore, since LLPS formation and IDP conformational changes are salt-dependent phenomena we have investigated by MD simulations the influence of salt concentration in shaping the conformational ensemble of the N-TER region of TFIP11. Increasing the salt concentration enhances the flexibility of the TFIP11 N-TER conformation, which presents a fuzzier conformational landscape, a more globular shape, and an unstructured arrangement that could favor LLPS segregation and protein-RNA interaction

Sound Factory

Le livre Sound Factory a reçu le soutien de la Sacem et de l’université Paris 8.Il est publié conjointement par les éditions Uqbar et Mélanie Seteun. Lire en ligne Consulter l’ouvrage gratuitement en ligne sur le site OpenBooks. Stéphane Dorin (dir.), Sound Factory Présentation “D’une révolution à l’autre”. C’est le titre que Jeremy Deller avait choisi pour son exposition au Palais de Tokyo afin de souligner les liens inattendus entre le déclin de l’industrie manufacturière et la naissance de..

Sound Factory

Le livre Sound Factory a reçu le soutien de la Sacem et de l’université Paris 8.Il est publié conjointement par les éditions Uqbar et Mélanie Seteun. Stéphane Dorin (dir.), Sound Factory Présentation “D’une révolution à l’autre”. C’est le titre que Jeremy Deller avait choisi pour son exposition au Palais de Tokyo afin de souligner les liens inattendus entre le déclin de l’industrie manufacturière et la naissance de l’industrie musicale. Les contributions de chercheurs en sciences sociales, ré..

Non-canonical role for the BAF complex subunit DPF3 in mitosis and ciliogenesis.

peer reviewedDPF3, along with other subunits, is a well-known component of the BAF chromatin remodeling complex that plays a key role in regulating chromatin remodeling activity and gene expression. Here, we elucidated a non-canonical localization and role for DPF3. We showed that DPF3 dynamically localizes to the centriolar satellites in interphase and in centrosome, spindle midzone/bridging fiber area and midbodies during mitosis. Loss of DPF3 causes K-fiber instability, unstable kinetochore-microtubules attachment and defects in chromosome alignment, thus resulting in altered mitotic progression, cell death and genomic instability. In addition, we also demonstrated that DPF3 localizes in centriolar satellites at the basis of primary cilia and is required for ciliogenesis by regulating axoneme extension. Together, these findings uncover a moonlighting dual function for DPF3 during mitosis and ciliogenesis