Albert LaSpada, MD, PhD, FACMGG
University of California Irvine
Alternative polyadenylation is a key feature of transcriptome dysregulation in ALS.
Dysregulation of RNA metabolism is a defining feature of ALS, resulting from the nuclear clearance of the RNA-binding protein TDP-43. TDP-43 is known to bind to its target pre-mRNAs near polyadenylation signals; however, this key aspect of TDP-43 function has not been thoroughly investigated in the context of ALS. By applying a new computational analysis pipeline to published ALS datasets, we recently identified hundreds of genes that are alternatively polyadenylated in ALS model systems. Characterization of this alternative polyadenylation, together with directed study of these genes, many of which function in pathways implicated in ALS pathogenesis, could lead to the discovery of novel ALS therapy targets.