NXF2 is involved in cytoplasmic mRNA dynamics through interactions with motor proteins.

NXF2 is involved in cytoplasmic mRNA dynamics through interactions with motor proteins.
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DOI:
10.1093/nar/gkm125
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发表时间:
2007
影响因子:
14.9
通讯作者:
Yoneda Y
Yoneda Y
中科院分区:
生物学2区
文献类型:
--
作者:
Takano K;Miki T;Katahira J;Yoneda Y

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Tap/NXF 1是进化上保守的NXF(核RNA输出因子)蛋白家族的创始成员,是大量poly(A)+RNA的核输出所必需的。在小鼠中,迄今为止已经鉴定和表征了另外三种NXF家族基因(NXF 2、NXF 3、NXF 7)。累积数据表明,NXF家族成员不仅在核mRNA输出中发挥作用,而且在转录后mRNA代谢的各个方面发挥作用。为了更好地了解NXF 2的功能作用,我们通过酵母双杂交筛选寻找其结合伴侣,并鉴定了包括KIF 17在内的几种胞质马达蛋白。NXF 2与KIF 17的相互作用通过GST下拉和免疫共沉淀试验证实,是由NXF 2的N-末端结构域介导的,这是初级神经元树突中点状定位模式所需的。我们还发现,NXF 2的树突状颗粒,这是共定位与KIF 17,mRNA和Staufen 1,一个已知的神经元mRNA颗粒的组成部分,双向移动沿着树突微管依赖性的方式。这些结果表明,NXF 2,一个核质mRNA转运蛋白,通过与细胞质马达蛋白的相互作用,在mRNA的细胞质定位中发挥额外的作用。
Tap/NXF1, the founding member of the evolutionarily conserved NXF (Nuclear RNA export Factor) family of proteins, is required for the nuclear export of bulk poly(A)+ RNAs. In mice, three additional NXF family genes (NXF2, NXF3, NXF7) have been identified and characterized to date. Cumulative data suggest that NXF family members play roles, not only in nuclear mRNA export, but also in various aspects of post-transcriptional mRNA metabolism. In order to better understand the functional role of NXF2, we searched for its binding partners by yeast two-hybrid screening and identified several cytoplasmic motor proteins, including KIF17. The interaction of NXF2 with KIF17, which was confirmed by GST pull-down and co-immunoprecipitation assays, is mediated by the N-terminal domain of NXF2, which is required for the punctate localization patterns in dendrites of primary neurons. We also found that the NXF2-containing dendritic granules, which were co-localized with KIF17, mRNA and Staufen1, a known component of neuronal mRNA granules, moved bidirectionally along dendrites in a microtubule-dependent manner. These results suggest that NXF2, a nucleo-cytoplasmic mRNA transporter, plays additional roles in the cytoplasmic localization of mRNAs through interactions with cytoplasmic motor proteins.
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