Viral Regulation of mRNA Export

Recent advances have led to an understanding of how eukaryotic mRNAs are exported from the nucleus to the cytoplasm. This process involves an elaborate machinery that is conserved from yeasts to humans and is coupled to upstream events in RNA metabolism. Eukaryotic pre-mRNAs are processed after synthesis in the nucleus by capping at the 5′ end, cleavage and polyadenylation to form the 3′ end, and splicing to remove intervening sequences. Following processing, mRNAs must be exported through the nuclear pore complex (NPC) to the cytoplasm for translation, which requires recognition by export factors to direct the mRNAs to nuclear export receptors for translocation through the NPC (17, 81, 108). A large body of evidence shows that TAP/NXF1, in conjunction with its heterodimeric partner, p15/NXT, is the nuclear export receptor for mRNAs in metazoans (5, 27, 33, 45, 48, 107) (Table ​(Table1).1). The yeast homologue of TAP/NXF1, termed Mex67p, has been shown to function as the mRNA export receptor in yeasts (44, 88, 91, 101). TAP/NXF1 and Mex67p have been shown to shuttle between the nucleus and cytoplasm, cross-link to poly(A)+ RNA, localize at the nuclear pores, and interact directly with nucleoporins (5, 37, 45, 88, 91). Further, overexpression of TAP/NXF1 in Xenopus oocytes or mammalian cells stimulated mRNA export (5, 37), and inactivation of TAP/NXF1 in Caenorhabditis elegans (103) and Drosophila (38) by RNA interference blocked nuclear export of poly(A)+ RNA, indicating a direct role in mRNA export.