Characterizing the Alu-induced transcriptome, proteome, and secretome in human fibroblasts

Transposable elements (TEs) are mobile genetic elements that constitute large fractions of eukaryotic genomes (~38-45% of the mouse and human genomes, respectively). In humans, the two most abundant TEs are Long Interspersed Element-1 (LINE-1 or L1) and Alu. These are implicated in a number of aging-related phenotypes, including genome instability, mitochondrial dysfunction, and senescence. Here, we electroporate IMR-90 and WI-38 fibroblasts with Alu overexpressing plasmids (and their corresponding controls). The objective of this study is to 1) determine if known senescence markers are secreted by cells overexpressing Alu and 2) globally characterize transcriptomic and proteomic changes associated with elevated Alu expression. Though some senescence markers have been observed in L1-related senescence (IL1B, CCL2, IL6, and MMP3), a comprehensive analysis of TE-associated secreted factors remains to be conducted, and no published data exist regarding Alu-induced factors. This information will clarify the molecular mechanisms by which transposons may promote cellular senescence, specifically, and cellular dysfunction, generally, and open new avenues for therapeutic intervention.