REFs bind directly RNA and NXF1 or Me圆7p, facilitating the recruitment of NXF1 or Me圆7p to cellular mRNAs. Among these are members of the REF protein family ( Stutz et al., 2000).
Instead, the protein Mtr2p is predicted to be functionally analogous to p15 in this organism ( Katahira et al., 1999).īinding of the NXF1:p15 heterodimers to mRNA export cargoes is thought to be mediated by adaptor proteins. 15 kD), is conserved in metazoa but not in Saccharomyces cerevisiae. 70 kD) belongs to the conserved family of NXF proteins, which includes yeast Me圆7p, Caenorhabditis elegans, Drosophila melanogaster (Dm), * and human NXF1 (also known as TAP Herold et al., 2000). The larger subunit of the heterodimer (ca. mRNA export is mediated by a heterodimeric export receptor, distinct from the importin β–like family of nuclear transport receptors ( Conti and Izaurralde, 2001 Dreyfuss et al., 2002 Lei and Silver, 2002 Reed and Hurt, 2002). Recent studies in yeast and higher eukaryotes have led to the elucidation of an evolutionarily conserved pathway for the export of bulk mRNA to the cytoplasm. Our results imply that the essential role of UAP56 in mRNA export is not restricted to the recruitment of REF1. Because a significant fraction of bulk mRNA is detected in the cytoplasm of cells depleted of all EJC proteins, we conclude that additional adaptor protein(s) mediate the interaction between NXF1 and cellular mRNAs in metazoa.
Only when REF1 and RNPS1 are codepleted, or when all EJC proteins are simultaneously depleted is a partial nuclear accumulation of polyadenylated RNAs observed. Contrary to expectation, we show that REF1 and the additional components of the EJC are dispensable for export of bulk mRNA in Drosophila cells. An essential role for metazoan REF1 or the additional EJC proteins in this process has not been established. NXF1 and UAP56 are essential for mRNA export. REF1 is a component of the exon–exon junction complex (EJC) thus, the EJC is thought to play a role in the export of spliced mRNA. The metazoan proteins UAP56, REF1, and NXF1 are thought to bind sequentially to mRNA to promote its export to the cytoplasm: UAP56 is thought to recruit REF1 to nascent mRNA REF1 acts as an adaptor protein mediating the association of NXF1 with mRNA, whereas NXF1 translocates the mRNA across the nuclear pore complex.
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