Christopher R. Brown

TL;DR: It is shown that transcriptional activation of the GAL genes results in their association with nuclear pore proteins, relocation to the nuclear periphery, and loss of RanGEF association, which indicates that the organization of the genome is coupled via transcriptional state to thenuclear transport machinery.

TL;DR: Examination of changes in nuclear organization that accompany stimulus by the mating pheromone alpha factor found that most alpha-factor-induced genes become associated with components of the nuclear envelope and the myosin-like protein Mlp1, which has been implicated in mRNA export, was further shown to exhibit RNA dependence in its association with alpha-Factor- induced genes.

TL;DR: It is shown that inhibiting HDACs leads to significant changes in genomic organization, recruiting regions of transcriptional regulation to mammalian nuclear pore complexes, including the recruitment of promoter regions, euchromatin-rich domains, and differentially expressed genes.

TL;DR: Liver exposure data indicate that the improvement in potency is predominantly due to increased metabolic stability of the siRNA conjugates, and this work employed an iterative screening approach across multiple siRNAs to arrive at advanced designs with low 2′-deoxy-2′-fluoro content that yield significantly improved potency and duration in preclinical species, including non-human primate.

TL;DR: Compared two siRNAs of the same sequence but with different modification pattern resulting in different degrees of protection against nuclease activity enhanced stability translated into substantially improved liver exposure, gene silencing efficacy and duration of effect in mice.