Differential subcellular distributions and trafficking functions of hnRNP A2/B1 spliceoforms.
Differential subcellular distributions and trafficking functions of hnRNP A2/B1 spliceoforms.
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DOI：
10.1111/j.1600-0854.2010.01072.x
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发表时间：
2010-07-01
期刊：
影响因子：
--
通讯作者：
Smith R
中科院分区：
文献类型：
--
作者：
Han SP;Friend LR;Carson JH;Korza G;Barbarese E;Maggipinto M;Hatfield JT;Rothnagel JA;Smith R
在神经细胞中，mRNA分子从细胞核向远端突起的运输由hnRNP A2/B1反式作用因子介导。虽然hnRNP A2/B1选择性剪接产生4种亚型，但大多数功能研究没有区分这些亚型。在这里，我们表明，使用同种型特异性抗体和同种型特异性GFP融合表达构建体，A2 b是神经细胞中的主要胞质同种型，这表明它可能在mRNA运输中发挥关键作用。单个亚型的差异亚细胞分布模式由替代外显子的存在或不存在确定，所述替代外显子也影响它们在不同细胞区室中的动态行为，如通过荧光相关光谱法测量的。A2 b的表达也随年龄、物种和细胞发育而差异调节。此外，共注射同种型特异性抗体和标记的RNA到活的少突胶质细胞中显示RNA颗粒的组装通过阻断A2 b功能而受损。这些发现表明，神经细胞调节mRNA运输通过调节hnRNP A2/B1的选择性剪接和控制A2 b的表达水平，这可能是胞质运输功能的主要介质。这些发现强调了考虑选择性剪接蛋白的异构体特异性功能的重要性。
Trafficking of mRNA molecules from the nucleus to distal processes in neural cells is mediated by hnRNP A2/B1 trans-acting factors. Although hnRNP A2/B1 is alternatively spliced to generate 4 isoforms, most functional studies have not distinguished among these isoforms. Here we show, using isoform-specific antibodies and isoform-specific GFP-fusion expression constructs, that A2b is the predominant cytoplasmic isoform in neural cells, suggesting that it may play a key role in mRNA trafficking. The differential subcellular distribution patterns of the individual isoforms are determined by the presence or absence of alternative exons that also affect their dynamic behavior in different cellular compartments, as measured by fluorescence correlation spectroscopy. Expression of A2b is also differentially regulated with age, species and cellular development. Furthermore, co-injection of isoform-specific antibodies and labeled RNA into live oligodendrocytes shows that assembly of RNA granules is impaired by blockade of A2b function. These findings suggest that neural cells modulate mRNA trafficking by regulating alternative splicing of hnRNP A2/B1 and controlling expression levels of A2b, which may be the predominant mediator of cytoplasmic trafficking functions. These findings highlight the importance of considering isoform-specific functions for alternatively spliced proteins.
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影响因子：
4.8
作者：
Shan, JG;Moran-Jones, K;Smith, B
通讯作者：
Smith, B
影响因子：
4
作者：
He, YW;Brown, MA;Smith, R
通讯作者：
Smith, R
DOI：
10.1007/s00018-008-8532-1
发表时间：
2009-04
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
He Y;Smith R
通讯作者：
Smith R
影响因子：
16.2
作者：
Kanai, Y;Dohmae, N;Hirokawa, N
通讯作者：
Hirokawa, N
影响因子：
3.5
作者：
Hatfield, JT;Rothnagel, JA;Smith, R
通讯作者：
Smith, R