Back to Search
Start Over
The Antagonistic Gene Paralogs Upf3a and Upf3b Govern Nonsense-Mediated RNA Decay
- Source :
- Cell, vol 165, iss 2
- Publication Year :
- 2016
- Publisher :
- eScholarship, University of California, 2016.
-
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.
- Subjects :
- 0301 basic medicine
Evolution
1.1 Normal biological development and functioning
Nonsense-mediated decay
Duplicate
Repressor
Embryonic Development
RNA-binding protein
Biology
Medical and Health Sciences
General Biochemistry, Genetics and Molecular Biology
Article
Gametogenesis
Cell Line
Evolution, Molecular
03 medical and health sciences
Mice
0302 clinical medicine
Genes, Duplicate
Underpinning research
Cell Line, Tumor
Gene duplication
Genetics
Animals
Humans
RNA, Messenger
Gene
Tumor
Mechanism (biology)
RNA
RNA-Binding Proteins
Molecular
Biological Sciences
Stem Cell Research
Nonsense Mediated mRNA Decay
030104 developmental biology
Fertility
Genes
Hela Cells
Adaptation
030217 neurology & neurosurgery
HeLa Cells
Developmental Biology
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Cell, vol 165, iss 2
- Accession number :
- edsair.doi.dedup.....f4b01daff41886d701445b7ae1f3d3a4