TDP-43 stabilises the processing intermediates of mitochondrial transcripts Academic Article uri icon

abstract

  • The 43-kDa trans-activating response region DNA-binding protein 43 (TDP-43) is a product of a causative gene for amyotrophic lateral sclerosis (ALS). Despite of accumulating evidence that mitochondrial dysfunction underlies the pathogenesis of TDP-43-related ALS, the roles of wild-type TDP-43 in mitochondria are unknown. Here, we show that the small TDP-43 population present in mitochondria binds directly to a subset of mitochondrial tRNAs and precursor RNA encoded in L-strand mtDNA. Upregulated expression of TDP-43 stabilised the processing intermediates of mitochondrial polycistronic transcripts and their products including the components of electron transport and 16S mt-rRNA, similar to the phenotype observed in cells deficient for mitochondrial RNase P. Conversely, TDP-43 deficiency reduced the population of processing intermediates and impaired mitochondrial function. We propose that TDP-43 has a novel role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts.

authors

  • Izumikawa, Keiichi
  • Nobe, Yuko
  • Yoshikawa, Harunori
  • Ishikawa, Hideaki
  • Miura, Yutaka
  • Nakayama, Hiroshi
  • Nonaka, Takashi
  • Hasegawa, Masato
  • Egawa, Naohiro
  • Inoue, Haruhisa
  • Nishikawa, Kouki
  • Yamano, Koji
  • Simpson, Richard J
  • Taoka, Masato
  • Yamauchi, Yoshio
  • Isobe, Toshiaki
  • Takahashi, Nobuhiro

publication date

  • 2017