Pathogenic Mutation of TDP-43 Impairs RNA Processing in a Cell Type-Specific Manner: Implications for the Pathogenesis of ALS/FTLD.

ABSTRACT: Transactivating response element DNA-binding protein of 43 kDa (TDP-43), which is encoded by the TARDBP gene, is an RNA-binding protein with fundamental RNA processing activities, and its loss-of-function (LOF) has a central role in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TARDBP mutations are postulated to inactivate TDP-43 functions, leading to impaired RNA processing. However, it has not been fully examined how mutant TDP-43 affects global RNA regulation, especially in human cell models. Here, we examined global RNA processing in forebrain cortical neurons derived from human induced pluripotent stem cells (iPSCs) with a pathogenic TARDBP mutation encoding the TDP-43^K263E protein. In neurons expr

SUBMITTER: Imaizumi K 

PROVIDER: S-EPMC9186108 | biostudies-literature | 2022 May-Jun

REPOSITORIES: biostudies-literature