The C-terminal domain of TAP interacts with the nuclear pore complex and promotes export of specific CTE-bearing RNA substrates

Messenger RNAs are exported from the nucleus as large ribonucleoprotein com plexes (mRNPs). To date, proteins implicated in this process include TAP/Me x67p and RAE1/Gle2p and are distinct from the nuclear transport receptors o f the beta-related, Ran-binding protein family. Mex67p is essential for mRN A export in yeast, Its vertebrate homolog TAP has been implicated in the ex port of cellular mRNAs and of simian type D viral RNAs bearing the constitu tive transport element (CTE), Here we show that TAP is predominantly locali zed in the nucleoplasm and at both the nucleoplasmic and cytoplasmic faces of the nuclear pore complex (NPC), TAP interacts with multiple components o f the NPC including the nucleoporins CAN, Nup98, Nup153, p62, and with thre e major NPC subcomplexes, The nucleoporin-binding domain of TAP comprises r esidues 508-619, In HeLa cells, this domain is necessary and sufficient to target GFP-TAP fusions to the nuclear rim, Moreover, the isolated domain st rongly competes multiple export pathways in vivo, probably by blocking bind ing sites on the NPC that are shared with other transport receptors, Microi njection experiments implicate this domain in the export of specific CTE-co ntaining RNAs, Finally, we show that TAP interacts with transportin and wit h two proteins implicated in the export of cellular mRNAs: RAE1/hGle2 and E 1B-AP5, The interaction of TAP with nucleoporins, its direct binding to the CTE RNA, and its association with two mRNP binding proteins suggest that T AP is an RNA export mediator that may bridge the interaction between specif ic RNP export substrates and the NPC.