The Epstein–Barr virus (EBV)-encoded latent membrane protein-1 (LMP1), a functional homologue of the tumor necrosis factor receptor family, substantially contributes to EBV's oncogenic potential by activating nuclear factor-κB (NF-κB). miR-155 is an oncogenic miRNA critical for B-cell maturation and immunoglobulin production in response to antigen. We report that miR-155 expression is much higher in EBV-immortalized B cells than in EBV-negative B cells. LMP1, but not LMP2, up-regulated the expression of miR-155, when transfected in EBV-negative B cells. We analyzed two putative NF-κB binding sites in the miR-155 promoter; both sites recruited NF-κB complex, in nuclear extract from EBV-immortalized cells. The exogenous expression of LMP1, in EBV-negative background, is temporally correlated to induction of p65 with binding on both NF-κB sites and with miR-155 overexpression. The induction of p65 binding together with increased RNA polymerase II binding, confirms that LMP1-mediated activation of miR-155 occurs transcriptionally. In reporter assays, miR-155 promoter lacking NF-κB binding sites was no longer activated by LMP1 expression and an intact AP1 site is needed to attain maximum activation. Finally, we demonstrate that LMP1-mediated activation of miR-155 in an EBV-negative background correlates with reduction of protein PU.1, which is a possible miR target.

The expression of the RNA-binding factor Fragile X mental retardation protein (FMRP) is disrupted in the most common inherited form of cognitive deficiency in humans. FMRP controls neuronal morphogenesis by mediating the translational regulation and localization of a large number of mRNA targets, and these functions are closely associated with transport of FMRP complexes within neurites by microtubule-based motors. However, the mechanisms that link FMRP to motors and regulate its transport are poorly understood. Here we show that FMRP is complexed with Bicaudal-D (BicD) through a domain in the latter protein that mediates linkage of cargoes with the minus-end-directed motor dynein. We demonstrate in Drosophila that the motility and, surprisingly, levels of FMRP protein are dramatically reduced in BicD mutant neurons, leading to a paucity of FMRP within processes. We also provide functional evidence that BicD and FMRP cooperate to control dendritic morphogenesis in the larval nervous system. Our findings open new perspectives for understanding localized mRNA functions in neurons.