This entry represents the RNA recognition motif (RRM)-like domain in Upf3B, a human orthologue of yeast Upf3p and Caenorhabditis elegans SMG-4 []. It derives from X-linked gene UPF3B and is required for nonsense-mediated mRNA decay (NMD) in human []. Upf3B is a nucleocytoplasmic shuttling protein that associates selectively with spliced beta-globin mRNA in vivo []. Like other Upf3 proteins, Upf3B contains nuclear import and export signals, and a conserved domain with some similarity to an RNA recognition motif (RRM), indicating that it may be an RNA binding protein.
This entry includes nonsense-mediated mRNA decay protein 3 (Upf3) and its homologues. In budding yeasts, Upf3 is involved in the nonsense-mediated mRNA decay (NMD) pathway []. Human Upf3a and Upf3b are components of the exon-junction complex (EJC), which promotes nonsense-mediated mRNA decay (NMD) and regulate translation efficiency [].
This entry includes Nmd2 from yeasts and UPF2 from animals. They are involved in the nonsense-mediated mRNA decay (NMD) pathway [, ]. In the human UPF complex (composed of UPF1/2/3), UPF2 and UPF3b cooperatively stimulate both ATPase and RNA helicase activities of UPF1 [].
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism by which eukaryotic cells detect and degrade transcripts containing premature termination codons. Three 'up-frameshift' proteins, UPF1, UPF2 and UPF3, are essential for this process in organisms ranging from yeast, human to plants []. Exon junction complexes (EJCs) are deposited ~24 nucleotides upstream of exon-exon junctions after splicing. Translation causes displacement of the EJCs, however, premature translation termination upstream of one or more EJCs triggers the recruitment of UPF1, UPF2 and UPF3 and activates the NMD pathway [, ]. This entry contains UPF3. The crystal structure of the complex between human UPF2 and UPF3b, which are, respectively, a MIF4G (middle portion of eIF4G) domain and an RNP domain (ribonucleoprotein-type RNA-binding domain) has been determined to 1.95A. The protein-protein interface is mediated by highly conserved charged residues in UPF2 and UPF3b and involves the β-sheet surface of the UPF3b ribonucleoprotein (RNP) domain, which is generally used by these domains to bind nucleic acids. In UPF3b the RNP domain does not bind RNA, whereas the UPF2 construct and the complex do. It is clear that some RNP domains have evolved for specific protein-protein interactions rather than as nucleic acid binding modules [].
