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

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 â the generation of antagonistic functions. One product of this duplication event â UPF3B â is critical for the nonsense-mediated RNA decay (NMD) pathway, while its autosomal counterpart â UPF3A â 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 âhyperâ NMD and display defects in embryogenesis and gametogenesis, consistent with UPF3A serving as a molecular rheostat that directs developmental events. â Examination of transcript stability with loss of UPF3A in mouse P19 cells.

ORGANISM(S): Mus musculus

SUBMITTER: Miles Wilkinson

PROVIDER: E-GEOD-77262 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Project description: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.

2016-03-31 | GSE77262 | GEO

Deciphering the cellular roles and dissecting functional regions of UPF3A and UPF3B in human NMD

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2022-04-25 | E-MTAB-10716 | biostudies-arrayexpress

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Project description:UPF3A and UPF3B are paralogous genes in human cells that are involved in the nonsense-mediated decay (NMD) pathway. NMD is a cellular quality control mechanism that monitors mRNAs during translation. Aberrant translation due to features such as the presence of a premature stop codon downstream on an exon-exon junction activates NMD and leads to the degradation of the mRNA. To investigate the role of UPF3B and UPF3A in NMD, we have generated UPF3B knockout human Flp-In T-REx 293 cells using CRISPR-Cas9. We generated RNA-Sequencing data for wildtype and UPF3B KO cells with additional siRNA-mediated knockdown of Luciferase (Luc) as control or UPF3A.

2022-04-25 | E-MTAB-10711 | biostudies-arrayexpress

Genome-wide consequences of compromised NMD and their relavence for variable clinical phenotype of patients with UPF3B mutations [CNV]

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Genome-wide consequences of compromised NMD and their relavence for variable clinical phenotype of patients with UPF3B mutations [RNA-seq]

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Genome-wide consequences of compromised NMD and their relavence for variable clinical phenotype of patients with UPF3B mutations [mRNA profiling]

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