Nuclear RNA export factor 7 is localized in processing bodies and neuronal RNA granules through interactions with shuttling hnRNPs

Nuclear RNA export factor 7 is localized in processing bodies and neuronal RNA granules through interactions with shuttling hnRNPs
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DOI:
10.1093/nar/gkm556
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发表时间:
2008-02-01
影响因子:
14.9
通讯作者:
Yoneda, Yoshihiro
Yoneda, Yoshihiro
中科院分区:
生物学2区
文献类型:
--
作者:
Katahira, Jun;Miki, Takashi;Yoneda, Yoshihiro

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核RNA输出因子(NXF)家族蛋白质已经涉及转录后基因表达的各个方面。该研究表明,小鼠NXF 7表现出异源定位,即NXF 7与翻译核糖体、应激颗粒(SG)和加工体(P-体)缔合,后两者被认为是mRNA的储存、降解和/或分选的细胞质位点。通过酵母双杂交筛选,一系列异质核核糖核蛋白(hnRNP)被确定为NXF 7的可能结合伴侣。其中,hnRNP A3被认为参与某些mRNA的翻译控制和/或细胞质定位,在体外与NXF 7形成稳定的复合物。虽然hnRNP A3与翻译核糖体无关,但它与NXF 7共定位于P体中。暴露于氧化应激后,NXF 7反式定位于SGs,而hnRNPA 3没有。在分化的神经母细胞瘤Neuro 2a细胞中,NXF 7与hnRNP A3共定位于细胞体和神经突中。NXF 7的氨基末端的一半,这是需要稳定的复合物形成与hnRNP A3,正好与P-体和神经元RNA颗粒的本地化所需的区域。这些发现表明NXF 7通过与hnRNPA 3相互作用在mRNA的分选、运输和/或储存中起作用。
The nuclear RNA export factor (NXF) family proteins have been implicated in various aspects of post-transcriptional gene expression. This study shows that mouse NXF7 exhibits heterologous localization, i.e. NXF7 associates with translating ribosomes, stress granules (SGs) and processing bodies (P-bodies), the latter two of which are believed to be cytoplasmic sites of storage, degradation and/or sorting of mRNAs. By yeast two-hybrid screening, a series of heterogeneous nuclear ribonucleoproteins (hnRNPs) were identified as possible binding partners for NXF7. Among them, hnRNP A3, which is believed to be involved in translational control and/or cytoplasmic localization of certain mRNAs, formed a stable complex with NXF7 in vitro. Although hnRNP A3 was not associated with translating ribosomes, it was co-localized with NXF7 in P-bodies. After exposing to oxidative stress, NXF7 trans-localized to SGs, whereas hnRNP A3 did not. In differentiated neuroblastoma Neuro2a cells, NXF7 was co-localized with hnRNP A3 in cell body and neurites. The amino terminal half of NXF7, which was required for stable complex formation with hnRNP A3, coincided with the region required for localization in both P-bodies and neuronal RNA granules. These findings suggest that NXF7 plays a role in sorting, transport and/or storage of mRNAs through interactions with hnRNP A3.