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研究発表を行った学会；
・第３４回　日本分子生物学会年会
　２０１１年１２月１３日〜１６日（横浜）

タイトル；Nucleocytoplasmic transport is involved in nuclear architecture regulation.

発表者；斉藤　典子　氏
　　　（熊本大学　発生医学研究所　細胞医学分野）
Abstract；
Mammalian nuclei are functionally compartmentalized to facilitate efficient nuclear events. Nuclear speckle/interchromatin granule cluster is one of the most prominent nuclear domains, and enriched with factors involved in RNA metabolism. It can be visualized with marker antibody SC35/3C5 which recognizes phosphorylated SR splicing factors. Nuclear speckle is implicated in gene expression and often found adjacent to the site of active transcription. In an animal body, formation of nuclear speckle is developmentally regulated. In certain cases including spermatids in mouse testis, SC35 antigens are absent from the nucleus and instead localized as granulated structures in the cytoplasm. To investigate how the nuclear architecture is formed in the cell, we performed a phenotypic screen using HeLa cells treated with series of small interfering RNAs. Depletion of nuclear transport factors including RAN, RANBP2, RCC1 or TNPO3 commonly induced cytoplasmic granules, similar to the one in the testis, which we termed cytoplasmic granules (CGs). Detailed analyses of CGs suggested that a specific step in a sequential nuclear entry of speckle components at late mitosis was disrupted. Cells with CGs have imbalanced distribution of phosphorylated- and hypophosphorylated forms of SR proteins, which affects alternative splicing pattern. We propose that regulated nucleocytoplasmic transport at the transition of mitosis and G1 is critical for proper nuclear speckle formation and alternative splicing in next cell cycle. Interestingly, RanBP2 is down regulated during spermatogenesis in mouse testis where alternative splicing is prevalent; suggesting the similar molecular mechanism in vivo.