Characterizing the RNA targets and position-dependent splicing regulation by TDP-43

TDP-43 is a RNA-binding protein that forms inclusion bodies in ALS. The authors show that TDP-43 preferentially binds long clusters of UG-rich sequences and that TDP-43 binding on pre-mRNAs influences alternative splicing. Many alternative mRNA isoforms regulated by TDP-43 encode proteins that regulate neuronal development or are implicated in neurological diseases. TDP-43 is a predominantly nuclear RNA-binding protein that forms inclusion bodies in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The mRNA targets of TDP-43 in the human brain and its role in RNA processing are largely unknown. Using individual nucleotide-resolution ultraviolet cross-linking and…