RT Journal Article SR Electronic T1 UPF3A is dispensable for nonsense-mediated mRNA decay in mouse pluripotent and somatic cells JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202201589 DO 10.26508/lsa.202201589 VO 6 IS 6 A1 Chengyan Chen A1 Yanmin Shen A1 Luqian Li A1 Yaoxin Ren A1 Zhao-Qi Wang A1 Tangliang Li YR 2023 UL https://www.life-science-alliance.org/content/6/6/e202201589.abstract AB Nonsense-mediated mRNA decay (NMD) is a highly conserved regulatory mechanism of post-transcriptional gene expression 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 the NMD machinery. Although 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. Through extensive analysis on the expressions of 33 NMD targets, we found UPF3A neither represses NMD in mouse embryonic stem cells, somatic cells, nor in major organs including the liver, spleen, and thymus. Our study reinforces that UPF3A is dispensable for NMD when UPF3B is present. Furthermore, UPF3A may weakly and selectively promote NMD in certain murine organs.