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05 28, 2024;7 (1): 654.

Effect of nonsense-mediated mRNA decay factor SMG9 deficiency on premature aging in zebrafish.

Shaohong Lai, Hiroshi Shiraishi, Wulan Apridita Sebastian, Nobuyuki Shimizu, Ryohei Umeda, Mayo Ikeuchi, Kyoko Kiyota, Takashi Takeno, Shuya Miyazaki, Shinji Yano, Tatsuo Shimada, Akihiko Yoshimura, Reiko Hanada, Toshikatsu Hanada
Author Information
  1. Shaohong Lai: Department of Cell Biology, Oita University Faculty of Medicine, Yufu, Oita, Japan.
  2. Hiroshi Shiraishi: Department of Cell Biology, Oita University Faculty of Medicine, Yufu, Oita, Japan.
  3. Wulan Apridita Sebastian: Department of Pediatrics, Oita University Faculty of Medicine, Yufu, Oita, Japan.
  4. Nobuyuki Shimizu: Department of Cell Biology, Oita University Faculty of Medicine, Yufu, Oita, Japan. ORCID
  5. Ryohei Umeda: Department of Neurophysiology, Oita University Faculty of Medicine, Yufu, Oita, Japan.
  6. Mayo Ikeuchi: Department of Cell Biology, Oita University Faculty of Medicine, Yufu, Oita, Japan.
  7. Kyoko Kiyota: Department of Cell Biology, Oita University Faculty of Medicine, Yufu, Oita, Japan.
  8. Takashi Takeno: Department of Cell Biology, Oita University Faculty of Medicine, Yufu, Oita, Japan.
  9. Shuya Miyazaki: Department of Cell Biology, Oita University Faculty of Medicine, Yufu, Oita, Japan.
  10. Shinji Yano: Institute for Research Management, Oita University, Yufu, Oita, Japan.
  11. Tatsuo Shimada: Oita Medical Technology School, Japan College of Judo-Therapy, Acupuncture & Moxibustion Therapy, Oita, Japan.
  12. Akihiko Yoshimura: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
  13. Reiko Hanada: Department of Neurophysiology, Oita University Faculty of Medicine, Yufu, Oita, Japan.
  14. Toshikatsu Hanada: Department of Cell Biology, Oita University Faculty of Medicine, Yufu, Oita, Japan. thanada@oita-u.ac.jp. ORCID
PMID: 38806677 DOI: 10.1038/s42003-024-06356-6

Abstract

SMG9 is an essential component of the nonsense-mediated mRNA decay (NMD) machinery, a quality control mechanism that selectively degrades aberrant transcripts. Mutations in SMG9 are associated with heart and brain malformation syndrome (HBMS). However, the molecular mechanism underlying HBMS remains unclear. We generated smg9 mutant zebrafish (smg9) that have a lifespan of approximately 6 months or longer, allowing for analysis of the in vivo function of Smg9 in adults in more detail. smg9 zebrafish display congenital brain abnormalities and reduced cardiac contraction. Additionally, smg9 zebrafish exhibit a premature aging phenotype. Analysis of NMD target mRNAs shows a trend toward increased mRNA levels in smg9 zebrafish. Spermidine oxidase (Smox) is increased in smg9 zebrafish, resulting in the accumulation of byproducts, reactive oxygen species, and acrolein. The accumulation of smox mRNA due to NMD dysregulation caused by Smg9 deficiency leads to increased oxidative stress, resulting in premature aging.

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Grants

  1. 20H03644/MEXT | Japan Society for the Promotion of Science (JSPS)
  2. 21K06871/MEXT | Japan Society for the Promotion of Science (JSPS)

MeSH Term

Animals
Zebrafish
Nonsense Mediated mRNA Decay
Aging, Premature
Zebrafish Proteins
RNA, Messenger
Oxidative Stress
Mutation

Chemicals

Zebrafish Proteins
RNA, Messenger
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

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