@article{52034b6ec7764e40ac6959368641a299,
title = "The Antagonistic Gene Paralogs Upf3a and Upf3b Govern Nonsense-Mediated RNA Decay",
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.",
author = "Shum, {Eleen Y.} and Jones, {Samantha H.} and Ada Shao and Chousal, {Jennifer N.} and Krause, {Matthew D.} and Chan, {Wai Kin} and Lou, {Chih Hong} and Espinoza, {Josh L.} and Song, {Hye Won} and Phan, {Mimi H.} and Madhuvanthi Ramaiah and Lulu Huang and McCarrey, {John R.} and Peterson, {Kevin J.} and {De Rooij}, {Dirk G.} and Heidi Cook-Andersen and Wilkinson, {Miles F.}",
note = "Funding Information: This work was supported by the NIH (GM111838, HD001259, and K12 HD001259), the Howard Hughes Medical Institute, and the Interfaces Scholar program, Reproductive Health Research grant (K12 HD001259). The authors thank Jens Lykke-Andersen (UCSD), Sebastien Durand (UCSD), and Mary Ann Handel (Jackson Laboratories) for their valuable scientific input, antibodies, and samples. Funding Information: This work was supported by the NIH (GM111838, HD001259, and K12 HD001259), the Howard Hughes Medical Institute, and the Interfaces Scholar program, Reproductive Health Research grant (K12 HD001259). The authors thank Jens Lykke-Andersen (UCSD), Sebastien Durand (UCSD), and Mary Ann Handel (Jackson Laboratories) for their valuable scientific input, antibodies, and samples. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = apr,
day = "7",
doi = "10.1016/j.cell.2016.02.046",
language = "English (US)",
volume = "165",
pages = "382--395",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}