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• W2516520158 abstract "Nonsense-mediated RNA decay is an evolutionarily conserved RNA quality control pathway designed to protect cells from genetic aberrances as well as to modulate normal gene expression during development. Many proteins have been identified that function in NMD, including UPF3B, which is encoded by an X-linked gene that causes intellectual disability when mutated in humans. In this study, I examined the role of both UPF3B and its autosomal paralog, UPF3A, in a well-established system for studying neural development: the olfactory epithelium. Using knockout mouse models deficient in UPF3A, UPF3B, or both, I obtained evidence as to the molecular and physiological roles of these factors in the development of olfactory sensory neurons. I found that conditional loss of UPF3A in OSNs resulted in a shift in OSN markers suggestive of a depletion of OSN stem cells and an over-accumulation of mature OSNs. This provided evidence that UPF3A controls the balance of OSN stem cell renewal and differentiation. Examination of NMD substrates in Upf3a-conditional KO (cKO) OE in vivo revealed that UPF3A has the opposite function as UPF3B - it represses NMD. Consistent with the opposing roles of UPF3A and UPF3B, genetic disruption of both these factors partially rescued defects present in single mutants. This supports a model in which UPF3A and UPF3B together form a molecular rheostat that controls the magnitude of NMD and thereby the stability of transcripts crucial for normal neural development. These results implicate the UPF3 proteins as potentially useful therapeutic targets to correct some neuro-developmental disorders" @default.
• W2516520158 created "2016-09-16" @default.
• W2516520158 creator A5019304725 @default.
• W2516520158 date "2014-01-01" @default.
• W2516520158 modified "2023-09-27" @default.
• W2516520158 title "The Role of UPF Proteins in Nonsense-Mediated Decay and in Neurogenesis" @default.
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• W2516520158 hasPublicationYear "2014" @default.
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