PLX123886

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

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

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