Molecular determinants of nucleolar translocation of RNA helicase A
Molecular determinants of nucleolar translocation of RNA helicase A
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DOI：
10.1016/j.yexcr.2007.07.037
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发表时间：
2007-10-15
影响因子：
3.7
通讯作者：
Tang, Hengli
中科院分区：
文献类型：
--
作者：
Liu, Zhe;Kenworthy, Rachael;Tang, Hengli
RNA解旋酶A（RHA）是DNA/RNA解旋酶DEAH盒家族的成员，参与多种细胞过程和许多病毒的生命周期。RHA的亚细胞定位是动态的，尽管其在核质中的稳态浓度。我们以前已经表明，它穿梭迅速细胞核和细胞质之间的凭借一个双向核运输结构域（NTD）位于其羧基末端。在这里，我们调查的分子决定其易位的核内，更具体地说，它的再分配从核质核仁或核仁周围区域。我们发现，低温处理，转录抑制或复制的丙型肝炎病毒引起的蛋白质的核内重新分布，这表明RHA穿梭于核仁和核质之间，并成为被困在核仁或核仁周围区域后，封锁运输到核质。NTD和ATP酶活性是RHA转运到核仁或核仁周围区所必需的。其中一个双链RNA结合域（dsRBD II）也需要这种核仁易位（NoT）表型。RNA干扰研究表明，RHA是培养的肝癌细胞的生存所必需的，ATP酶活性似乎是重要的这一关键作用。(C)2007年爱思唯尔公司All rights reserved.
RNA helicase A (RHA) is a member of the DEAH-box family of DNA/RNA helicases involved in multiple cellular processes and the life cycles of many viruses. The subcellular localization of RHA is dynamic despite its steady-state concentration in the nucleoplasm. We have previously shown that it shuttles rapidly between the nucleus and the cytoplasm by virtue of a bidirectional nuclear transport domain (NTD) located in its carboxyl terminus. Here, we investigate the molecular determinants for its translocation within the nucleus and, more specifically, its redistribution from the nucleoplasm to nucleolus or the perinucleolar region. We found that low temperature treatment, transcription inhibition or replication of hepatitis C virus caused the intranuclear redistribution of the protein, suggesting that RHA shuttles between the nucleolus and nucleoplasm and becomes trapped in the nucleolus or the perinucleolar region upon blockade of transport to the nucleoplasm. Both the NTD and ATPase activity were essential for RHA's transport to the nucleolus or perinucleolar region. One of the double-stranded RNA binding domains (dsRBD II) was also required for this nucleolar translocation (NoT) phenotype. RNA interference studies revealed that RHA is essential for survival of cultured hepatoma cells and the ATPase activity appears to be important for this critical role. (C) 2007 Elsevier Inc. All rights reserved.