TDP-43 toxicity and the usefulness of junk

Abstract

A new study shows that loss of the lariat debranching enzyme Dbr1 suppresses TDP-43 toxicity. The accumulated intronic lariat RNAs, which are normally degraded after splicing, likely act as decoys to sequester TDP-43 away from binding to and disrupting functions of other RNAs.

Figure 1

Model for suppressing TDP-43 toxicity by loss of Dbr1. (a) Dbr1 normally converts intronic lariats into linear RNAs that are subsequently degraded by exonucleases. Cytoplasmic TDP-43 aggregates sequester normal RNAs/RNA-binding proteins, thereby reducing their function. (b) Without Dbr1, lariats accumulate cytoplasmically, sequestering TDP-43 and diminishing its interference with normal RNAs.