We know of two pathways for nuclear export of RNAs. Incompletely spliced Mason?Pfizer monkey virus transcripts bind the nuclear export factor TAP through a consensus transport element (CTE), and are targeted to the nuclear pore by direct interaction between TAP and the FG-repeats of a set of nucleoporins. A similar pathway is probably used for global nuclear export of cellular mRNAs, although it is a mystery how these bind to TAP. Incompletely spliced human immunodeficiency virus-1 transcripts, on the other hand, bind to the viral protein Rev. Rev, in turn, interacts with the exportin Crm1, which targets the transcripts to a different set of nucleoporins.

NXF3 is a close homologue of TAP, but it has deletions in the carboxy-terminal nucleoporin-binding domain as well as in the central CTE-binding domain, raising doubts as to whether it can act as an export factor. Yang et al. now report in Molecular Cell that NXF3 can be UV-crosslinked in vivo with endogenous poly(A+) RNA, that it shuttles between the nucleus and the cytoplasm, and that it can act as an export factor when bound artificially to RNAs. But surprisingly, when the authors used a binding assay they found that instead of interacting directly with nucleoporins like TAP, NXF3 interacts with NUP214 and RAB/hRIP ? a binding profile characteristic of Rev in this assay. Like Rev, NXF3 binds to Crm1 through a leucine-rich nuclear-export signal.

So, despite having 52% identity with TAP and a similar cellular function, NXF3 uses an entirely different molecular mechanism. But whereas TAP is ubiquitous and probably involved in the export of most cellular RNAs, NXF3 is mostly expressed in testis, suggestive of a tissue- and possibly RNA-specific function.