Staufen1 is imported into the nucleolus via a bipartite nuclear localization signal and several modulatory determinants.
Mammalian Stau1 (Staufen1), a modular protein composed of several dsRBDs (double-stranded RNA-binding domains), is probably involved in mRNA localization. Although Stau1 is mostly described in association with the rough endoplasmic reticulum and ribosomes in the cytoplasm, recent studies suggest that it may transit through the nucleus/nucleolus. Using a sensitive yeast import assay, we show that Stau1 is actively imported into the nucleus through a newly identified bipartite nuclear localization signal. As in yeast, the bipartite nuclear localization signal is necessary for Stau1 nuclear import in mammalian cells. It is also required for Stau1 nucleolar trafficking. However, Stau1 nuclear transit seems to be regulated by mechanisms that involve cytoplasmic retention and/or facilitated nuclear export. Cytoplasmic retention is mainly achieved through the action of dsRBD3, with dsRBD2 playing a supporting role in this function. Similarly, dsRBD3, but not its RNA-binding activity, is critical for Stau1 nucleolar trafficking. The function of dsRBD3 is strengthened or stabilized by the presence of dsRBD4 but prevented by the interdomain between dsRBD2 and dsRBD3. Altogether, these results suggest that Stau1 nuclear trafficking is a highly regulated process involving several determinants. The presence of Stau1 in the nucleus/nucleolus suggests that it may be involved in ribonucleoprotein formation in the nucleus and/or in other nuclear functions not necessarily related to mRNA transport.
Martel
Catherine
C
Department of Biochemistry, University of Montreal, P.O. Box 6128, Station Centre Ville, Montreal, Canada H3C 3J7.
Macchi
Paolo
P
Furic
Luc
L
Kiebler
Michael A
MA
Desgroseillers
Luc
L
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism; D002466:Cell Nucleolus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D002352:Carrier Proteins; D019913:Nuclear Localization Signals; D016601:RNA-Binding Proteins; C117884:staufen protein, mammalian