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Howard Hughes Medical Institute, and Department of Biochemistry and Biophysics, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania 19104-6148
Heterogeneous nuclear ribonucleoprotein
(hnRNP) A1 is an abundant nuclear protein that plays
an important role in pre-mRNA processing and mRNA
export from the nucleus. A1 shuttles rapidly between
the nucleus and the cytoplasm, and a 38-amino acid domain, M9, serves as the bidirectional transport signal of
A1. Recently, a 90-kD protein, transportin, was identified as the mediator of A1 nuclear import. In this study,
we show that transportin mediates the nuclear import
of additional hnRNP proteins, including hnRNP F. We
have also isolated and sequenced a novel transportin
homolog, transportin2, which may differ from
transportin1 in its substrate specificity. Immunostaining
shows that transportin1 is localized both in the cytoplasm and the nucleoplasm, and nuclear rim staining is
also observed. The nuclear localization of A1 is dependent on ongoing RNA polymerase II transcription. Interestingly, a pyruvate kinase-M9 fusion, which normally localizes in the nucleus, also accumulates in the
cytoplasm when RNA polymerase II is inhibited. Thus,
M9 itself is a specific sensor for transcription-dependent nuclear transport. Transportin1-A1 complexes
can be isolated from the cytoplasm and the nucleoplasm, but transportin1 is not detectable in hnRNP
complexes. RanGTP causes dissociation of A1-transportin1 complexes in vitro. Thus, it is likely that
after nuclear import, A1 dissociates from transportin1
by RanGTP and becomes incorporated into hnRNP
complexes, where A1 functions in pre-mRNA processing.
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