Caspases shutdown nonsense-mediated mRNA decay during apoptosis.
Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance mechanism that plays integral roles in eliminating mRNAs with premature termination codons to prevent the synthesis of truncated proteins that could be pathogenic. One response to the accumulation of detrimental proteins is apoptosis, which involves the activation of enzymatic pathways leading to protein and nucleic acid cleavage and culminating in cell death. It is not clear whether NMD is required to ensure the accurate expression of apoptosis genes or is no longer necessary since cytotoxic proteins are not an issue during cell death. The present study shows that caspases cleave the two NMD factors UPF1 and UPF2 during apoptosis impairing NMD. Our results demonstrate a new regulatory pathway for NMD that occurs during apoptosis and provide evidence for role of the UPF cleaved fragments in apoptosis and NMD inhibition.
Université de Lille, FRE 3642, Lille, France.|CNRS UMR 8161, Institut de Biologie de Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
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Jia
Université de Lille, FRE 3642, Lille, France.|CNRS UMR 8161, Institut de Biologie de Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
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Furlan
Unité Biologie et Pathogénicité Fongiques, Institut Pasteur, 25 rue du Dr Roux, Paris, France.
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Gonzalez-Hilarion
Université de Lille, FRE 3642, Lille, France.|CNRS UMR 8161, Institut de Biologie de Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
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Leroy
Department of Otolaryngology-Head and Neck Surgery, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Helen Diller Family Comprehensive Cancer Center, Institute for Human Genetics, Cardiovascular Research Institute, University of California, San Francisco, CA, USA.|Department of Pediatrics, University of Vermont College of Medicine, Burlington, VT, USA.
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Gruenert
Université de Lille, FRE 3642, Lille, France.|CNRS UMR 8161, Institut de Biologie de Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
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Tulasne
Université de Lille, FRE 3642, Lille, France.|CNRS UMR 8161, Institut de Biologie de Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
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Lejeune
D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D059365:Nonsense Mediated mRNA Decay / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D034741:RNA, Small Interfering; D020169:Caspases