title: The abnormal processing of TDP-43 is not an upstream event of reduced ADAR2 activity in ALS motor neurons.
abstract: TDP-43 pathology in motor neurons is a hallmark of ALS. In addition, the reduced expression of an RNA editing enzyme, adenosine deaminase acting on RNA 2 (ADAR2), increases the expression of GluA2 with an unedited Q/R site in the motor neurons of patients with sporadic ALS. As the occurrence of these two disease-specific abnormalities in the same motor neurons suggests a molecular link between them, we examined the effects of altered TDP-43 processing on ADAR2 activity in TetHeLaG2m and Neuro2a cells. We found that ADAR2 activity did not consistently change due to the overexpression or knockdown of TDP-43 or the expression of abnormal TDP-43, including caspase-3-cleaved fragments, truncated TDP-43 lacking either nuclear localization or export signals and ALS-linked TDP-43 mutants. These results suggest that the abnormal processing of TDP-43 is not an upstream event of inefficient GluA2 Q/R site editing in the motor neurons of sporadic ALS patients.
authors.affiliation: CREST, Japan Science and Technology Agency, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Takenari
authors.initials: T
authors.lastname: Yamashita
authors.forename: Takuto
authors.initials: T
authors.lastname: Hideyama
authors.forename: Sayaka
authors.initials: S
authors.lastname: Teramoto
authors.forename: Shin
authors.initials: S
authors.lastname: Kwak
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism*; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D046188:Protein Modification, Translational / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase