A cytoplasmic quaking I isoform regulates the hnRNP F/H-dependent alternative splicing pathway in myelinating glia.
A cytoplasmic quaking I isoform regulates the hnRNP F/H-dependent alternative splicing pathway in myelinating glia.
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DOI：
10.1093/nar/gku353
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发表时间：
2014-06
影响因子：
14.9
通讯作者：
Feng Y
中科院分区：
文献类型：
--
作者：
Mandler MD;Ku L;Feng Y
选择性RNA结合蛋白quaking I（QKI）在控制选择性剪接（AS）中起重要作用。三种QKI亚型广泛表达，显示出不同的核质分布。然而，QKI亚型控制AS的分子机制，特别是在不同的细胞类型中，仍然难以捉摸。quakingviable（qv-grafik ziel ="PIWIS04b4b480004880048888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888我们发现，细胞质异构体QKI-6调节OL中含多鸟嘌呤（G-run）转录物的AS，并通过抑制两种典型剪接因子（异源核核糖核蛋白（hnRNP）F和H）的表达来挽救qKI突变体中的异常AS。此外，我们确定了一个广谱的体内功能性hnRNP F/H目标的OL含有保守的外显子两侧的G-运行，其中许多是失调的qvod突变体。有趣的是，AS目标的QKI-6-hnRNP F/H途径在OLs的差异影响SWC，表明额外的细胞类型特异性因子调节AS在CNS和PNS髓鞘形成。总之，我们的研究提供了第一个证据，细胞质QKI-6的行为上游的hnRNP F/H，这形成了一个新的途径，以控制AS髓鞘神经胶质细胞。
The selective RNA-binding protein quaking I (QKI) plays important roles in controlling alternative splicing (AS). Three QKI isoforms are broadly expressed, which display distinct nuclear-cytoplasmic distribution. However, molecular mechanisms by which QKI isoforms control AS, especially in distinct cell types, still remain elusive. The quakingviable (qkv) mutant mice carry deficiencies of all QKI isoforms in oligodendrocytes (OLs) and Schwann cells (SWCs), the myelinating glia of central and peripheral nervous system (CNS and PNS), respectively, resulting in severe dysregulation of AS. We found that the cytoplasmic isoform QKI-6 regulates AS of polyguanine (G-run)-containing transcripts in OLs and rescues aberrant AS in the qkv mutant by repressing expression of two canonical splicing factors, heterologous nuclear ribonucleoproteins (hnRNPs) F and H. Moreover, we identified a broad spectrum of in vivo functional hnRNP F/H targets in OLs that contain conserved exons flanked by G-runs, many of which are dysregulated in the qkv mutant. Interestingly, AS targets of the QKI-6-hnRNP F/H pathway in OLs are differentially affected in SWCs, suggesting that additional cell-type-specific factors modulate AS during CNS and PNS myelination. Together, our studies provide the first evidence that cytoplasmic QKI-6 acts upstream of hnRNP F/H, which forms a novel pathway to control AS in myelinating glia.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
48
作者：
Katz, Yarden;Wang, Eric T.;Airoldi, Edoardo M.;Burge, Christopher B.
通讯作者：
Burge, Christopher B.
影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T
DOI：
10.1007/978-0-387-77374-2_8
发表时间：
2007-01-01
期刊：
ALTERNATIVE SPLICING IN THE POSTGENOMIC ERA
影响因子：
--
作者：
Martinez-Contreras, Rebeca;Cloutier, Philippe;Chabot, Benoit
通讯作者：
Chabot, Benoit
影响因子：
4.8
作者：
Paul, Sharan;Dansithong, Warunee;Reddy, Sita
通讯作者：
Reddy, Sita