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An alternative branch of the nonsense‐mediated decay pathway
Author(s) -
Chan WaiKin,
Huang Lulu,
Gudikote Jayanthi P,
Chang YaoFu,
Imam J Saadi,
MacLean James A,
Wilkinson Miles F
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601628
Subject(s) - biology , nonsense , nonsense mediated decay , genetics , computational biology , gene , rna , rna splicing
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 TCRβ 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 TCRβ NMD. Mapping experiments revealed the identity of TCRβ sequences that elicit a switch to UPF3b dependence. This regulation is not a peculiarity of TCRβ, 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.