EGF coordinates the nuclear and cytoplasmic activities of an RNA-binding protein to ensure a specific mRNA is translated at the right time and place in neurons, say Tsai et al.
mRNAs localize to specific regions within neurons, where they can be translated to quickly generate large amounts of a protein in the place where it is needed. Due to the large size of neurons, this is much more efficient than translating all mRNAs in a single place and then shipping out each protein to its site of action. But the movement and translation of these mRNAs must be tightly regulated, potentially by extracellular signals such as growth factors.
Tsai et al. discovered that EGF boosts expression of the κ-opioid receptor (KOR) by stimulating both the nuclear export and translation of KOR mRNA. The key to this dual control was an RNA-binding protein called Grb7. EGF prods a phosphatase called SHP-2 to dephosphorylate Grb7 in the nucleus, prompting it to bind KOR mRNA and recruit a protein complex involved in nuclear export. But EGF also stimulated focal adhesion kinase to rephosphorylate Grb7 in the cytoplasm, causing it to release the mRNA for translation into KOR protein.
Senior author Li-Na Wei is now investigating what happens in between nuclear exit and translation. mRNA is transported from the cell body to the axons, a process that is also likely to be regulated, perhaps by signals other than EGF. The researchers are also interested to discover the signals that regulate the localization and translation of other mRNAs.