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Molecular and Cellular Biology, July 2003, p. 4805-4813, Vol. 23, No. 14
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.14.4805-4813.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Rapid Deadenylation Triggered by a Nonsense Codon Precedes Decay of the RNA Body in a Mammalian Cytoplasmic Nonsense-Mediated Decay Pathway

Chyi-Ying A. Chen and Ann-Bin Shyu*

Department of Biochemistry and Molecular Biology, The University of Texas Houston Medical School, Houston, Texas 77030

Received 13 March 2003/ Returned for modification 10 April 2003/ Accepted 22 April 2003

Nonsense-mediated mRNA decay (NMD) is an RNA surveillance pathway that detects and destroys aberrant mRNAs containing nonsense or premature termination codons (PTCs) in a translation-dependent manner in eukaryotes. In yeast, the NMD pathway bypasses the deadenylation step and directly targets PTC-containing messages for decapping, followed by 5'-to-3' exonuclease digestion of the RNA body. In mammals, most PTC-containing mRNAs are subject to active nucleus-associated NMD. Here, using two distinct transcription-pulsing approaches to monitor mRNA deadenylation and decay kinetics, we demonstrate the existence of an active cytoplasmic NMD pathway in mammalian cells. In this pathway, a nonsense codon triggers accelerated deadenylation that precedes decay of the PTC-containing mRNA body. Transcript is stabilized when accelerated deadenylation is impeded by blocking translation initiation; by ectopically expressing two RNA-binding proteins, UNR and NSAP1; or by ectopically expressing a UPF1 dominant-negative mutant. These results are consistent with the notion that the nonsense codon can function in the cytoplasm by promoting rapid removal of the poly(A) tail as a necessary first step in the decay process.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, The University of Texas Houston Medical School, Houston, TX 77030. Phone: (713) 500-6068. Fax: (713) 500-0575. E-mail: Ann-Bin.Shyu{at}uth.tmc.edu.

Molecular and Cellular Biology, July 2003, p. 4805-4813, Vol. 23, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.14.4805-4813.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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