SRSF2 plays an unexpected role as reader of m5C on mRNA, linking epitranscriptomics to cancer.

A common mRNA modification is 5-methylcytosine (m5C), whose role in gene-transcript processing and cancer remains unclear. Here, we identify serine/arginine-rich splicing factor 2 (SRSF2) as a reader of m5C and impaired SRSF2 m5C binding as a potential contributor to leukemogenesis. Structurally, we identify residues involved in m5C recognition and the impact of the prevalent leukemia-associated mutation SRSF2P95H. We show that SRSF2 binding and m5C colocalize within transcripts. Furthermore, knocking down the m5C writer NSUN2 decreases mRNA m5C, reduces SRSF2 binding, and alters RNA splicing. We also show that the SRSF2P95H mutation impairs the ability of the protein to read m5C-marked mRNA, notably reducing its binding to key leukemia-related transcripts in leukemic cells. In leukemia patients, low NSUN2 expression leads to mRNA m5C hypomethylation and, combined with SRSF2P95H, predicts poor outcomes. Altogether, we highlight an unrecognized mechanistic link between epitranscriptomics and a key oncogenesis driver.

Versatile template-directed synthesis of gold nanocages with a predefined number of windows.

Highly symmetrical gold nanocages can be produced with a controllable number of circular windows of either 2, 3, 4, 6 or 12 via an original fabrication route. The synthetic pathway includes three main stages: the synthesis of silica/polystyrene multipod templates, the regioselective seeded growth of a gold shell on the unmasked part of the silica surface and the development of gold nanocages by dissolving/etching the templates. Electron microscopy and tomography provide evidence of the symmetrical features of the as-obtained nanostructures. The optical properties of nanocages with 4 and 12 windows were measured at the single particle level by spatial modulation spectroscopy and correlated with numerical simulations based on finite-element modeling. The new multi-step synthesis approach reported here also allows the synthesis of rattle-like nanostructures through filling of the nanocages with a guest nano-object. With the potential to adjust the chemical composition, size and geometry of both the guest particle and the host cage, it opens new routes towards the fabrication of hollow nanostructures of high interest for a variety of applications including sensing devices, catalytic reactors and biomedicine.

Large-scale lagovirus disease outbreaks in European brown hares (Lepus europaeus) in France caused by RHDV2 strains spatially shared with rabbits (Oryctolagus cuniculus).

Rabbit haemorrhagic disease virus (RHDV) is a lagovirus that causes rabbit haemorrhagic disease (RHD) in European rabbits (Oryctolagus cuniculus). In 2010, a new genotype called RHDV2 emerged in France. It exhibits a larger host range than classical RHDV strains by sporadically infecting different hare species, including the European hare (Lepus europaeus). Phylogenetic analyses revealed that closely related RHDV2 strains circulate locally in both hares and rabbits, and therefore that RHDV2 strains infecting hares do not belong to a lineage that has evolved only in this species. We showed that RHDV2 is widely distributed in France and that it was responsible for more than a third of cases of lagovirus disease in European hare populations in 2015. The oldest RHDV2 positive hare was sampled in November 2013 and we reported two hares co-infected by EBHSV and RHDV2. All together, our results raise important epidemiological and evolutionary issues. In particular, along with the potential emergence of recombinant EBHSV/RHDV2 strains in hares, the enlargement of the host range changes the host population structure of RHDV2 and may alter the impact of the virus on rabbit and hare populations.

Inhibition of SLC drug transporter activities by environmental bisphenols.

The plastic component bisphenol A (BPA) is suspected to exert deleterious effects towards human health and targets various cellular and molecular pathways, including activity of ATP-binding cassette drug transporters. The present study was designed to determine whether BPA and some derivatives, like its substitutes bisphenol F (BPF) and bisphenol S (BPS) and the flame retardant tetrabromobisphenol A (TBBPA), may additionally interact with solute carrier (SLC) drug transporters. Activities of the various following SLC transporters were inhibited in a major way (by >60%) by 100µM bisphenols: OCT1 and MATE1 (by BPA and TBBPA), OATP1B1 (by BPA, BPF and TBBPA), OATP1B3 and NTCP (by TBBPA) and OAT3 (by BPA, BPF, BPS and TBBPA); by contrast, activities of other transporters were not impacted (MATE2-K) or were stimulated (notably OCT1 by BPS and OCT2 by BPF). Transporter inhibitions due to bisphenols were concentrations-dependent, with half maximal inhibitory concentrations (IC50) ranging from 0.5µM to 73.5µM. BPA was finally shown to be not transported by OAT3, although inhibiting this transporter in a competitive manner. Taken together, these data indicate that bisphenols interact with SLC transporters, at concentration levels however rather higher than those occurring in humans in response to environmental exposure.

Synthesis of multivalent silica nanoparticles combining both enthalpic and entropic patchiness.

Silica particles with a controlled number of entropic patches, i.e. dimples, are synthesized through the growth of the silica core of binary multipods that have been produced by a seeded-growth emulsion polymerization reaction. Transmission electron microscopy studies indicate that the silica surface conforms to the shape of the polystyrene (PS) nodules of the multipods while growing, allowing good control of the final shape of the dimpled silica particles. The PS nodules are also used as protecting masks to regioselectively graft amino groups, as revealed by the adsorption of gold markers. After dissolution of the PS nodules, some polymer chains remain grafted onto the silica surface, forming organic bumps. These residues are also selectively functionalized, leading to silica particles with both entropic and enthalpic patches.

Synthesis and site-specific functionalization of tetravalent, hexavalent, and dodecavalent silica particles.

Different shapes: Tetravalent, hexavalent, and dodecavalent silica particles were obtained by the growth of the silica core of binary tetrapods, hexapods, and dodecapods, respectively. The surface of the multivalent particles can be regioselectively functionalized, thereby leading to particles with anisotropic geometry and chemistry.