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, consistent with UPF3A serving as a molecular rheostat that directs developmental events.      SOURCE: Miles Wilkinson (mfwilkinson@ucsd.edu) - Miles WIlkinson University of California, San Diego

Pluto Bioinformatics

GSE77262: RNA-seq of mouse P19 half-life samples upon loss of UPF3A