In eukaryotes, it is essential to have the ability to detect and degrade transcripts that lack full coding potential. Nonsense-mediated RNA decay (NMD) protects the organism by avoiding the translation of truncated peptides with dominant negative or deleterious gain-of-function potential. Rent1, a mammalian ortholog of Upflp, is essential for embryonic viability. Rent1 (also designated regulator of nonsense transcripts and HUpf1) contains an N-terminal zinc finger-like domain, NTPase domains and a region comprised of domains that define Rent1 as a superfamily group I helicase. Rent1 protein has nucleic-acid-dependent ATPase activity and 5′ to 3′ helicase activity. In addition, Rent1 is an RNA-binding protein whose activity is modulated by ATP and directly interacts with Rent2, which is a mammalian homolog of Upf2p. Two mammalian orthologs to Upf3p, Rent3a and Rent3b, are encoded by two separate genes. Rent3b (also known as Rent3X) is encoded by a X-linked gene and localizes primarily to the nucleus, while Rent1 and Rent2 localize primarily in the cytoplasm. Specific Rent3 protein interactions with Y14 and spliced mRNA suggest Rent3a and Rent3b serve as a link between splicing and NMD in the cytoplasm.
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