An NXF1 mRNA with a retained intron is expressed in hippocampal and neocortical neurons and is translated into a protein that functions as an Nxf1 cofactor.
An NXF1 mRNA with a retained intron is expressed in hippocampal and neocortical neurons and is translated into a protein that functions as an Nxf1 cofactor.
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带有保留内含子的 NXF1 mRNA 在海马和新皮质神经元中表达，并被翻译成充当 Nxf1 辅因子的蛋白质。
DOI：
10.1091/mbc.e16-07-0515
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发表时间：
2016
影响因子：
3.3
通讯作者：
Hammarskjold,Marie-Louise
中科院分区：
文献类型：
--
作者：
Li,Ying;Bor,Yeou-Cherng;Fitzgerald,MarkP;Lee,KevinS;Rekosh,David;Hammarskjold,Marie-Louise
Nxf1蛋白是mRNA转运的主要核输出受体，也是携带保留内含子的逆转录病毒mRNA输出所必需的。在后一种情况下，它与称为组成型转运元件（CTE）的RNA元件结合，并与称为Nxt1的辅因子一起发挥作用。NXF1基因还通过使用内含子10内的功能性CTE来调节其自身的含内含子RNA的表达。含有这个内含子的mRNA被输出到细胞质，在那里它可以被翻译成356个氨基酸的短Nxf1（sNxf1）蛋白，尽管它是无义介导的衰变（NMD）的主要候选者。在这里，我们证明，sNxf1是高度表达的细胞核和树突的海马和新皮层神经元在啮齿动物的大脑。此外，我们发现，sNxf1定位在RNA颗粒中的神经突分化的N2a小鼠神经母细胞瘤细胞，在那里它显示部分共定位与Staufen2亚型SS，一种蛋白质已知发挥作用的树突mRNA运输。我们还表明，sNxf1形成异源二聚体与全长Nxf1和sNxf1可以取代Nxt1，以提高表达CTE的mRNA，并促进其协会与多聚核糖体。
The Nxf1 protein is a major nuclear export receptor for the transport of mRNA, and it also is essential for export of retroviral mRNAs with retained introns. In the latter case, it binds to RNA elements known as constitutive transport elements (CTEs) and functions in conjunction with a cofactor known as Nxt1. TheNXF1gene also regulates expression of its own intron-containing RNA through the use of a functional CTE within intron 10. mRNA containing this intron is exported to the cytoplasm, where it can be translated into the 356–amino acid short Nxf1(sNxf1) protein, despite the fact that it is a prime candidate for nonsense-mediated decay (NMD). Here we demonstrate that sNxf1 is highly expressed in nuclei and dendrites of hippocampal and neocortical neurons in rodent brain. Additionally, we show that sNxf1 localizes in RNA granules in neurites of differentiated N2a mouse neuroblastoma cells, where it shows partial colocalization with Staufen2 isoform SS, a protein known to play a role in dendritic mRNA trafficking. We also show that sNxf1 forms heterodimers in conjunction with the full-length Nxf1 and that sNxf1 can replace Nxt1 to enhance the expression of CTE-containing mRNA and promote its association with polyribosomes.