Abstract
Gene duplication is a major evolutionary force driving adaptation and speciation, as it allows for the acquisition of new functions and can augment or diversify existing functions. Here, we report a gene duplication event that yielded another outcome - the generation of antagonistic functions. One product of this duplication event - UPF3B - is critical for the nonsense-mediated RNA decay (NMD) pathway, while its autosomal counterpart - UPF3A - encodes an enigmatic protein previously shown to have trace NMD activity. Using loss-of-function approaches in vitro and in vivo, we discovered that UPF3A acts primarily as a potent NMD inhibitor that stabilizes hundreds of transcripts. Evidence suggests that UPF3A acquired repressor activity through simple impairment of a critical domain, a rapid mechanism that may have been widely used in evolution. Mice conditionally lacking UPF3A exhibit "hyper" NMD and display defects in embryogenesis and gametogenesis. Our results support a model in which UPF3A serves as a molecular rheostat that directs developmental events.
Original language | English (US) |
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Pages (from-to) | 382-395 |
Number of pages | 14 |
Journal | Cell |
Volume | 165 |
Issue number | 2 |
DOIs | |
State | Published - Apr 7 2016 |
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology