Poly(A)-binding protein II (PABP2) is an abundant
nuclear protein that binds with high affinity to nascent
poly(A) tails, stimulating their extension and controlling
their length. In the cytoplasm, a distinct protein (PABP1)
binds to poly(A) tails and participates in mRNA translation
and stability. How cytoplasmic PABP1 substitutes for nuclear
PABP2 is still unknown. Here we report that PABP2 shuttles
back and forth between nucleus and cytoplasm by a carrier-mediated
mechanism. A potential novel type of nuclear localization
signal exists at the C-terminus of the protein, a domain
that is highly enriched in methylated arginines. PABP2
binds directly to transportin in a RanGTP-sensitive manner,
suggesting an involvement of this transport receptor in
mediating import of the protein into the nucleus. Although
PABP2 is small enough to diffuse passively through the
nuclear pores, protein fusion experiments reveal the existence
of a facilitated export pathway. Accordingly, no transport
of PABP2 to the cytoplasm occurs at 4 °C. In contrast,
export of PABP2 continues in the absence of transcription,
indicating that transport to the cytoplasm is independent
of mRNA traffic. Thus, rather than leaving the nucleus
as a passive passenger of mRNAs, the data suggest that
PABP2 interacts with the nuclear export machinery and may
therefore contribute to mRNA transport.