TY - JOUR
T1 - Effect of nonsense-mediated mRNA decay factor SMG9 deficiency on premature aging in zebrafish
AU - Lai, Shaohong
AU - Shiraishi, Hiroshi
AU - Sebastian, Wulan Apridita
AU - Shimizu, Nobuyuki
AU - Umeda, Ryohei
AU - Ikeuchi, Mayo
AU - Kiyota, Kyoko
AU - Takeno, Takashi
AU - Miyazaki, Shuya
AU - Yano, Shinji
AU - Shimada, Tatsuo
AU - Yoshimura, Akihiko
AU - Hanada, Reiko
AU - Hanada, Toshikatsu
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85194544154
U2 - 10.1038/s42003-024-06356-6
DO - 10.1038/s42003-024-06356-6
M3 - Article
C2 - 38806677
AN - SCOPUS:85194544154
SN - 2399-3642
VL - 7
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 654
ER -