PUBLICATION

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

Authors
Lai, S., Shiraishi, H., Sebastian, W.A., Shimizu, N., Umeda, R., Ikeuchi, M., Kiyota, K., Takeno, T., Miyazaki, S., Yano, S., Shimada, T., Yoshimura, A., Hanada, R., Hanada, T.
ID
ZDB-PUB-240529-10
Date
2024
Source
Communications biology   7: 654654 (Journal)
Registered Authors
Hanada, Reiko, Hanada, Toshikatsu
Keywords
none
MeSH Terms
  • Oxidative Stress
  • Aging, Premature*/genetics
  • Animals
  • Nonsense Mediated mRNA Decay*
  • Mutation
  • Zebrafish Proteins*/deficiency
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Zebrafish*/genetics
(all 11)
PubMed
38806677 Full text @ Commun Biol
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 (smg9oi7/oi7) 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. smg9oi7/oi7 zebrafish display congenital brain abnormalities and reduced cardiac contraction. Additionally, smg9oi7/oi7 zebrafish exhibit a premature aging phenotype. Analysis of NMD target mRNAs shows a trend toward increased mRNA levels in smg9oi7/oi7 zebrafish. Spermidine oxidase (Smox) is increased in smg9oi7/oi7 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.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
oi7
    Small Deletion
    oi8
      Indel
      oi13TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        smg8CRISPR1-smg8CRISPR
        smg9CRISPR1-smg9CRISPR
        smoxMO2-smoxMRPHLNO
        1 - 3 of 3
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        Fish
        No data available
        Antibodies
        No data available
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        1 - 1 of 1
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        Mapping
        No data available