論文

国際誌
2020年12月17日

Exosc2 deficiency leads to developmental disorders by causing a nucleotide pool imbalance in zebrafish.

Biochemical and biophysical research communications
  • Hiroyuki Yatsuka
  • Kazumasa Hada
  • Hiroshi Shiraishi
  • Ryohei Umeda
  • Ikuko Morisaki
  • Hirotaro Urushibata
  • Nobuyuki Shimizu
  • Wulan Apridita Sebastian
  • Takatoshi Hikida
  • Tohru Ishitani
  • Reiko Hanada
  • Tatsuo Shimada
  • Kenichi Kimoto
  • Toshiaki Kubota
  • Toshikatsu Hanada
  • 全て表示

533
4
開始ページ
1470
終了ページ
1476
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbrc.2020.10.044

Exosc2 is one of the components of the exosome complex involved in RNA 3' end processing and degradation of various RNAs. Recently, EXOSC2 mutation has been reported in German families presenting short stature, hearing loss, retinitis pigmentosa, and premature aging. However, the in vivo function of EXOSC2 has been elusive. Herein, we generated Exosc2 knockout (exosc2-/-) zebrafish that showed larval lethality 13 days post fertilization, with microcephaly, loss of spinal motor neurons, myelin deficiency, and retinitis pigmentosa. Mechanistically, Exosc2 deficiency caused impaired mRNA turnover, resulting in a nucleotide pool imbalance. Rapamycin, which modulated mRNA turnover by inhibiting the mTOR pathway, improved nucleotide pool imbalance in exosc2-/- zebrafish, resulting in prolonged survival and partial rescue of neuronal defects. Taken together, our findings offer new insights into the disease pathogenesis caused by Exosc2 deficiency, and might help explain fundamental molecular mechanisms in neuronal diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis, and spinal muscular atrophy.

リンク情報
DOI
https://doi.org/10.1016/j.bbrc.2020.10.044
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33333712
ID情報
  • DOI : 10.1016/j.bbrc.2020.10.044
  • PubMed ID : 33333712

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