Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay

Yamashita, Akio; Ohnishi, Tetsuo; Kashima, Isao; Taya, Yoichi; Ohno, Shigeo

doi:10.1101/gad.913001

Cited by 420RNA Research and SplicingRNA and protein synthesis mechanismsRNA regulation and disease

Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay

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Yamashita, Akio, Ohnishi, Tetsuo, Kashima, Isao, Taya, Yoichi, Ohno, Shigeo·2001·Genes & Development

DOI 10.1101/gad.913001PMC PMC312771

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Abstract

Nonsense-mediated mRNA decay (NMD) is a conserved surveillance mechanism that eliminates imperfect mRNAs that contain premature translation termination codons (PTCs) and code for nonfunctional or potentially harmful polypeptides. We show that a novel phosphatidylinositol 3-kinase-related protein kinase, hSMG-1, is a human ortholog of a product of Caenorhabditis elegans smg-1 , one of seven smg genes involved in NMD. hSMG-1 phosphorylates hUPF1/SMG-2 in vivo and in vitro at specific serine residues in SQ motifs. hSMG-1 can associate with hUPF1/SMG-2 and other components of the surveillance complex. In particular, overexpression of a kinase-deficient point mutant of hSMG-1, hSMG-1-DA, results in a marked suppression of the PTC-dependent β-globin mRNA degradation; whereas that of wild-type hSMG-1 enhances it. We also show that inhibitors of hSMG-1 induce the accumulation of truncated p53 proteins in human cancer cell lines with p53 PTC mutation. Taken together, we conclude that hSMG-1 plays a critical role in NMD through the direct phosphorylation of hUPF1/SMG-2 in the evolutionally conserved mRNA surveillance complex.

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Treatment of cells with caffeine leads to downregulation of SMG1, a member of the phosphatidylinositol 3-kinase-related protein kinase family, known to inhibit the phosphorylation of the core NMD factor UPF1, thereby blocking the NMD pathway.
“Treatment of cells with caffeine leads to downregulation of SMG1, a member of the phosphatidylinositol 3-kinase-related protein kinase family (Yamashita et al., 2001”
From Orchestrated Intron Retention Regulates Normal Granulocyte Differentiation (2013) · cites this paper as Yamashita et al., 2001

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Authors: Yamashita, A., Ohnishi, T., Kashima, I., Taya, Y., & Ohno, S.
Affiliations: Yokohama City University (JP)
National Cancer Center Research Institute (JP)
Corresponding author: Ohno, Shigeo
ORCID: Yamashita, Akio
Ohnishi, Tetsuo
Ohno, Shigeo
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 2001-09-01
Volume: 15
Issue: 17
Pages: 2215-2228
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.913001
PMC: PMC312771
OpenAlex: W2142812553
Cited by: 420
References: 46
Citations by year: 2026: 14 · 2025: 17 · 2024: 15 · 2023: 16 · 2022: 18 · 2021: 26 · 2020: 12 · 2019: 11 · 2018: 18 · 2017: 14 · 2016: 22 · 2015: 17 · 2014: 16 · 2013: 30 · 2012: 16
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Genes & Development (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Kihara Memorial Yokohama Foundation
Ministry of Education, Culture, Sports, Science and Technology
Japan Society for the Promotion of Science
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords: SMG1, nonsense-mediated mRNA decay, protein kinase phosphorylation, premature stop codon, cancer cell lines
MeSH terms: Amino Acid Sequence, Animals, Cell Line, Cloning, Molecular, Dose-Response Relationship, Drug, Multigene Family, Globins, HeLa Cells, Humans, Metalloendopeptidases, Models, Genetic, Molecular Sequence Data, Phosphorylation, Phylogeny, Plasmids, Precipitin Tests, Protein Binding, Protein Kinases, RNA, Messenger, Time Factors, Transfection, Protein Biosynthesis, Blotting, Northern, Caenorhabditis elegans, Protein Serine-Threonine Kinases, Sequence Homology, Amino Acid, DNA, Complementary, Phosphatidylinositol 3-Kinases, Protein Isoforms

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Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay

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