Proteins are transported into and out of the cell nucleus via specific signals. 
The two best-studied nuclear transport processes are mediated either by 
classical nuclear localization signals or nuclear export signals. There also are 
shuttling sequences that direct the bidirectional transport of RNA-binding 
proteins. Two examples are the M9 sequence in heterogeneous nuclear 
ribonucleoprotein A1 and the heterogeneous nuclear ribonucleoprotein K shuttling 
domain (KNS) sequence in heterogeneous nuclear ribonucleoprotein K, both of 
which appear to contribute importantly to the export of mRNA to the cytoplasm. 
HuR is an RNA-binding protein that can stabilize labile mRNAs containing AU-rich 
elements in their 3' untranslated regions and has been shown to shuttle between 
the nucleus and cytoplasm (18, 19). We have identified in HuR a shuttling 
sequence that also possess transcription-dependent nuclear localization signal 
activity. We propose that HuR first may bind AU-rich element-containing mRNAs in 
the nucleus and then escort them through the nuclear pore, providing protection 
during and after export to the cytoplasmic compartment.