An mRNA Nuclear Export Factor Regulates Itself
Biology is filled with feedback loops and other natural buffers to promote homeostasis. In the latest Nature, there is a ... cute ... paper about how the RNA export factor Tap (aka NXF1) mediates the nuclear export of an alternatively spliced form of it's own mRNA transcript. (For more background on the mechanism of nuclear export of mRNA, click here).
Viruses like the Mason-Pfizer monkey virus can exploit our mRNA export pathway by having their transcripts bind directly to export factors such as Tap. The RNA elements that bind Tap are called constitutive export elements (CTEs). In a hunt for CTEs in transcripts endogenous to the mammalian genome, the authors came up with a CTE in Tap's own transcript. Turns out that this CTE is only present in an alternatively spliced (and shorter) form of Tap. This small Tap has a RNA binding domain but lacks a domain that interacts with the nuclear pore complex thus disabling the protein's nuclear export capability.
This feedback loop may regulate Tap activity -- the more Tap activity one has, the more mRNA that encodes inactivated Tap is exported. Once synthesized, inactivated Tap may suppress Tap activity, however the exact mechanism remains unclear. One problem is that the small Tap remains cytosolic. Any ideas? From the paper:
... Although the function of the small Tap protein is unclear, it retains the RNA-binding domain but lacks the nucleoporin and NXT1-binding domains, and locates mainly to the cytoplasm. Thus, it may regulate the function of Tap at the translational level.
We'll have to see how the loose ends get tied up in this story.
Ying Li, Yeou-cherng Bor, Yukiko Misawa, Yuming Xue, David Rekosh and Marie-Louise Hammarskjöld
An intron with a constitutive transport element is retained in a Tap messenger RNA
Nature (2006) 443:234-237