Discovery - University of Dundee - Online Publications

Library & Learning Centre

TDP-43 stabilises the processing intermediates of mitochondrial transcripts

TDP-43 stabilises the processing intermediates of mitochondrial transcripts

Research output: Contribution to journalArticle

View graph of relations

Authors

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

Research units

Info

Original languageEnglish
Article number7709
Number of pages14
JournalScientific Reports
Volume7
DOIs
StatePublished - 9 Aug 2017

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.

Documents

Open Access permissions

Open

Documents

  • Publisher final version

    Final published version, 4 MB, PDF-document

    © The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

DOI

Library & Learning Centre

Contact | Accessibility | Policy