Molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43

TDP-43 regulates alternative splicing of the cystic fibrosis transmembrane regulator (CFTR) and is found in cytosolic granules associated with several neurodegenerative disorders. A new solution structure of the tandem RNA-recognition motifs (RRMs) that mediate interactions with its UG-rich RNA targets reveals a new RRM arrangement critical for TDP-43 function.