Upf3a is dispensable for nonsense-mediated mRNA decay in mouse pluripotent and somatic cells

Abstract: Nonsense-mediated mRNA decay (NMD) is a highly conserved post-transcriptional gene expression regulation mechanism in eukaryotic cells. NMD plays essential roles in mRNA quality and quantity control, and thus safeguards multiple biological processes including embryonic stem cell differentiation and organogenesis. UPF3A and UPF3B in vertebrate species, originated from a single UPF3 gene in yeast, are key factors in NMD machinery. While UPF3B is a well-recognized weak NMD promoting factor, whether UPF3A functions in promoting or suppressing NMD is under debate. In this study, we generated a Upf3a conditional knockout mouse strain, and established multiple lines of embryonic stem cells and somatic cells without Upf3a. We found Upf3a does not repress NMD in mouse embryonic stem cells, somatic cells and major organs including liver, spleen, and thymus. Our study reinforces that Upf3a is mainly dispensable for NMD and may weakly and selectively promote NMD in certain organs.