Identification and characterization of novel factors that act in the nonsense-mediated mRNA decay pathway in nematodes, flies and mammals

Nonsense‐mediated mRNA decay (NMD) is a surveillance mechanism that degrades mRNAs harboring premature termination codons (PTCs). We have conducted a genome‐wide RNAi screen in Caenorhabditis elegans that resulted in the identification of five novel NMD genes that are conserved throughout evolution. Two of their human homologs, GNL2 ( ngp‐1 ) and SEC13 ( npp‐20 ), are also required for NMD in human cells. We also show that the C. elegans gene noah‐2 , which is present in Drosophila melanogaster but absent in humans, is an NMD factor in fruit flies. Altogether, these data identify novel NMD factors that are conserved throughout evolution, highlighting the complexity of the NMD pathway and suggesting that yet uncovered novel factors may act to regulate this process. Synopsis A genome‐wide RNAi screen in C. elegans identifies five novel NMD genes that are required for development and conserved throughout evolution, suggesting that the regulation of the NMD pathway is more complex than previously thought. Five novel NMD factors that are also essential for development are identified in C. elegans . Two of the human orthologs, GNL2 ( ngp‐1 ) and SEC13 ( npp‐20 ), are also required for NMD in human cells. The C. elegans gene noah‐2 , which is present in Drosophila melanogaster but absent in humans, is a tissue‐specific NMD factor in fruit flies. Graphical Abstract A genome‐wide RNAi screen in C. elegans identifies five novel NMD genes that are required for development and conserved throughout evolution, suggesting that the regulation of the NMD pathway is more complex than previously thought.