Analysis of alternative splicing associated with aging and neurodegeneration in the human brain.

Age is the most important risk factor for neurodegeneration; however, the effects of aging and neurodegeneration on gene expression in the human brain have most often been studied separately. Here, we analyzed changes in transcript levels and alternative splicing in the temporal cortex of individuals of different ages who were cognitively normal, affected by frontotemporal lobar degeneration (FTLD), or affected by Alzheimer's disease (AD). We identified age-related splicing changes in cognitively normal individuals and found that these were present also in 95% of individuals with FTLD or AD, independent of their age.

Understanding splicing regulation through RNA splicing maps.

Alternative splicing is a highly regulated process that greatly increases the proteome diversity and plays an important role in cellular differentiation and disease. Interactions between RNA-binding proteins (RBPs) and pre-mRNA are the principle regulator of splicing decisions. Findings from recent genome-wide studies of protein-RNA interactions have been combined with assays of the global effects of RBPs on splicing to create RNA splicing maps.

Complex genetic changes in strains of Saccharomyces cerevisiae derived by selection in the laboratory.

Selection of model organisms in the laboratory has the potential to generate useful substrates for testing evolutionary theories. These studies generally employ relatively long-term selections with weak selective pressures to allow the accumulation of multiple adaptations. In contrast to this approach, we analyzed two strains of Saccharomyces cerevisiae that were selected for resistance to multiple stress challenges by a rapid selection scheme to test whether the variation between rapidly selected strains might also be useful in evolutionary studies.

C/EBP and Cdx family factors regulate liver fatty acid binding protein transgene expression in the small intestinal epithelium.

A transgene constructed from the rat liver fatty acid binding protein gene (Fabp1) promoter is active in all murine small intestinal crypt and villus epithelial cells. Coincident Cdx and C/EBP transcription factor binding sites were identified spanning Fabp1 nucleotides -90 to -78. CDX-1, CDX-2, C/EBPalpha, and C/EBPbeta activated the Fabp1 transgene in CaCo-2 cells, and mutagenizing the -78 site prevented activation by these factors.