Upf3a, an Up-frameshift protein 3 family member, is involved in the nonsense-mediated mRNA decay (NMD) pathway, a crucial post-transcriptional gene expression regulatory mechanism in eukaryotes [1,2,3,4,5,6]. NMD safeguards mRNA quality and quantity control, thus being essential for multiple biological processes such as embryonic stem cell differentiation, organogenesis, and tissue homeostasis [2]. Genetic models, especially mouse models, have been instrumental in studying Upf3a's function.

In mouse models, a conditional knockout (CKO) of Upf3a demonstrated that it is dispensable for NMD when Upf3B is present [2]. In human cells, co-depletion of Upf3A and Upf3B led to marked NMD inhibition, showing functional redundancy between the two factors [1]. In zebrafish, Upf3a was found to be essential for the genetic compensation response (GCR) induced by nonsense mutations in leg1 genes, independent of H3K4me3 [4]. In human colorectal cancer, high levels of Upf3a were associated with aggressiveness and poor prognosis, and knockdown of Upf3a in CRC cells led to a decline in migration potential [5].

In summary, Upf3a, through its role in the NMD pathway, has implications in multiple biological processes. The use of gene knockout and conditional knockout mouse models has provided valuable insights into its function, especially in relation to NMD, genetic compensation, and disease, such as colorectal cancer. Understanding Upf3a's function can potentially offer new strategies for disease treatment and prevention.