Erratum to: Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases (EMBO Molecular Medicine, (2016), 8, 11, (1265-1288), 10.15252/emmm.201505889)

10.15252/emmm.201707895EMBO Molecular Medicine9798

Hypoxic Regulation of Vascular Endothelial Growth Factor mRNA Stability Requires the Cooperation of Multiple RNA Elements

Vascular endothelial growth factor (VEGF) is a key regulator of developmental, physiological, and tumor angiogenesis. Upregulation of VEGF expression by hypoxia appears to be a critical step in the neovascularization of solid cancers. The VEGF mRNA is intrinsically labile, but in response to hypoxia the mRNA is stabilized. We have systematically analyzed the regions in the VEGF mRNA that are responsible for its lability under normoxic conditions and for stabilization in response to hypoxia. We find that the VEGF mRNA not only contains destabilizing elements in its 3′ untranslated region (3′UTR), but also contains destabilizing elements in the 5′UTR and coding region. Each region can independently promote mRNA degradation, and together they act additively to effect rapid degradation under normoxic conditions. Stabilization of the mRNA in response to hypoxia is completely dependent on the cooperation of elements in each of the 5′UTR, coding region, and 3′UTR. Combinations of any of two of these three regions were completely ineffective in responding to hypoxia, whereas combining all three regions allowed recapitulation of the hypoxic stabilization seen with the endogenous VEGF mRNA. We conclude that multiple regions in the VEGF mRNA cooperate both to ensure the rapid degradation of the mRNA under normoxic conditions and to allow stabilization of the mRNA in response to hypoxia. Our findings highlight the complexity of VEGF gene expression and also reveal a mechanism of gene regulation that could become the target for strategies of therapeutic intervention

Anderson localization in 1D systems with correlated disorder

Anderson localization has been a subject of intense studies for many years. In this context, we study numerically the influence of long-range correlated disorder on the localization behavior in one dimensional systems. We investigate the localization length and the density of states and compare our numerical results with analytical predictions. Specifically, we find two distinct characteristic behaviors in the vicinity of the band center and at the unperturbed band edge, respectively. Furthermore we address the effect of the intrinsic short-range correlations