UPF3A is a ubiquitously expressed NMD factor among mouse tissues

Abstract

Nonsense-mediated mRNA decay (NMD), an important post-transcriptional regulatory mechanism in gene expression, is actively involved in a series of cellular and physiological processes, thus controlling cell fate and tissue homeostasis. Defects in NMD cause human diseases such as neurodevelopmental disorders, tumorigenesis and autoimmunity. UPF3 (Up- frameshift protein 3), first identified in the bakers yeast, is a core NMD factor. UPF3A and UPF3B, the two UPF3 paralogs emerging in vertebrates, have either activating or suppressing roles in NMD. Previous studies found that UPF3B protein is ubiquitously expressed in almost all mammalian organs, while UPF3A protein is hardly detectable in most of mammalian tissues, except in the testis. One hypothesis explaining this phenomena is the functional antognism between UPF3A and UPF3B in NMD. Thus, UPF3B competitively binds to UPF2 with higher affinity than UPF3A, which finally destabilizes UPF3A protein. In the present study, we quantitatively evaluated the expression of UPF3A and UPF3B in nine major tissues and reproductive organs of wild type male and female mice. Our study confirmed that UPF3A has the highest expression in male germlines. To our surprise, we found in most tissues, including brain and thymus, the protein level of UPF3A is comparable with that of UPF3B. In spleen and lung, UPF3A is higher than UPF3B. These findings are further supported by publicly available gene expression data. Thus, our study demonstrated that UPF3A protein is ubiquitously expressed in mouse tissues, and may play important roles in the homeostasis of multiple mammalian tissues.