Nonsense-mediated mRNA decay (NMD) in animal embryogenesis: to die or not to die, that is the question

Nonsense-mediated mRNA decay (NMD) is a well-studied cellular quality-control pathway. It decreases the half-lives of eukaryotic mRNAs that aberrantly contain premature termination codons and additionally regulates an estimated 10–20% of normal transcripts. NMD factors play crucial roles during embryogenesis in many animals. Here, we review data indicating that NMD factors are required for proper embryogenesis by discussing the abnormal developmental phenotypes that result when the abundance of individual NMD factors is either downregulated or completely eliminated. We conclude that while NMD per se affects the embryogenesis of all animals, it is required to avoid embryonic lethality in only some animals. The critical roles of many NMD factors in other metabolic pathways undoubtedly also contribute to embryonic development if not viability.

► We present EJC-dependent and faux 3′-UTR mechanisms of NMD in eukaryotes.
► We highlight embryogenesis in animals: particularly worm, fly, fish, mouse and man.
► Abnormal embryonic phenotypes with particular NMD-factor deficiencies are noted.
► We present evidence for NMD-factor function in pathways other than NMD.
► We weight NMD versus such non-NMD pathway roles in embryogenesis/embryo viability.