title: A role for transportin in deposition of TTP to cytoplasmic RNA granules and mRNA decay.
abstract: Importin-beta family members, which shuttle between the nucleus and the cytoplasm, are essential for nucleocytoplasmic transport of macromolecules. We attempted to explore whether importin-beta family proteins change their cellular localization in response to environmental change. In this report, we show that transportin (TRN) was minimally detected in cytoplasmic processing bodies (P-bodies) under normal cell conditions but largely translocated to stress granules (SGs) in stressed cells. Fluorescence recovery after photobleaching analysis indicated that TRN moves rapidly in and out of cytoplasmic granules. Depletion of TRN greatly enhanced P-body formation but did not affect the number or size of SGs, suggesting that TRN or its cargo(es) participates in cellular function of P-bodies. Accordingly, TRN associated with tristetraprolin (TTP) and its AU-rich element (ARE)-containing mRNA substrates. Depletion of TRN increased the number of P-bodies and stabilized ARE-containing mRNAs, as observed with knockdown of the 5'-3' exonuclease Xrn1. Moreover, depletion of TRN retained TTP in P-bodies and meanwhile reduced the fraction of mobile TTP to SGs. Therefore, our data together suggest that TRN plays a role in trafficking of TTP between the cytoplasmic granules and whereby modulates the stability of ARE-containing mRNAs.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center and Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 11529, Taiwan.
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Chang
authors.forename: Woan-Yuh
authors.initials: WY
authors.lastname: Tarn
mesh_terms: D003594:Cytoplasmic Granules / Q000378:metabolism; D006801:Humans; D028884:Karyopherins / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D051816:Tristetraprolin / Q000378:metabolism*
chemical_list: D028884:Karyopherins; D012333:RNA, Messenger; D051816:Tristetraprolin