Article
- The EMBO Journal (2007) 26, 1820 - 1830
- doi:10.1038/sj.emboj.7601628
Published online: 15 March 2007
Subject Category:
An alternative branch of the nonsense-mediated decay pathway
Wai-Kin Chan1, Lulu Huang1, Jayanthi P Gudikote1, Yao-Fu Chang1, J Saadi Imam1, James A MacLean II1 and Miles F Wilkinson1
- Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Correspondence to:
Miles F Wilkinson, Department of Biochemistry and Molecular Biology, Unit 1000, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. Tel.: +1 713 563 3215; Fax: +1 713 563 3375; E-mail: mwilkins@mdanderson.org
Received 1 November 2006; Accepted 5 February 2007
Abstract
The T-cell receptor (TCR) locus undergoes programmed rearrangements that frequently generate premature termination codons (PTCs). The PTC-bearing transcripts derived from such nonproductively rearranged genes are dramatically downregulated by the nonsense-mediated decay (NMD) pathway. Here, we show that depletion of the NMD factor UPF3b does not impair TCR
NMD, thereby distinguishing it from classical NMD. Depletion of the related factor UPF3a, by itself or in combination with UPF3b, also has no effect on TCR NMD. Mapping experiments revealed the identity of TCR sequences that elicit a switch to UPF3b dependence. This regulation is not a peculiarity of TCR, as we identified many wild-type genes, including one essential for NMD, that transcribe NMD-targeted mRNAs whose downregulation is little or not affected by UPF3a and UPF3b depletion. We propose that we have uncovered an alternative branch of the NMD pathway that not only degrades aberrant mRNAs but also regulates normal mRNAs, including one that participates in a negative feedback loop controlling the magnitude of NMD.
Keywords:
- microarray,
- nonsense-mediated decay,
- T-cell receptor,
- UPF3
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