Regulation of alternative splicing within the supraspliceosome.
Regulation of alternative splicing within the supraspliceosome.
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DOI：
10.1016/j.jsb.2011.11.005
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发表时间：
2012-01
影响因子：
3
通讯作者：
Sperling, Ruth
中科院分区：
文献类型：
--
作者：
Sebbag-Sznajder, Naama;Raitskin, Oleg;Angenitzki, Minna;Sato, Taka-Aki;Sperling, Joseph;Sperling, Ruth
关键词：
选择性剪接是调控真核生物转录组的一个基本特征，因为大约95%的人类多外显子Pol II转录本都受到这一过程的影响。调控剪接通过正负调控信号的组合相互作用发挥作用，这些信号存在于Pre-mRNA中，由反式作用因子识别。所有这些RNA和蛋白质成分都被组装在一个巨大的、21个丙二醛的核糖核蛋白剪接机--超剪接体中。由于大多数选择性剪接的mRNA亚型在不同的细胞和组织类型之间存在差异，因此执行选择性剪接的能力被认为是构成体内剪接机器的超剪接小体的组成部分。在这里，我们证明了内源性人类PolII转录本的结构性和选择性剪接的mRNAs：hnRNP A/B、运动神经元的存活(SMN)和ADAR2主要存在于超复制小体中。这一发现与我们的观察一致，即剪接调控因子hnRNP G以及所有磷酸化的SR蛋白主要与超剪接体相关。我们进一步证明，hnRNP A/B的选择性剪接的变化，受到SRSF5(SRp40)上调或C6-神经酰胺处理的影响，发生在超复制体内。这些观察结果支持超剪接小体在剪接调控和选择性剪接中的作用。
Alternative splicing is a fundamental feature in regulating the eukaryotic transcriptome, as ~95% of multi-exon human Pol II transcripts are subject to this process. Regulated splicing operates through the combinatorial interplay of positive and negative regulatory signals present in the pre-mRNA, which are recognized by trans-acting factors. All these RNA and protein components are assembled in a gigantic, 21 MDa, ribonucleoprotein splicing machine – the supraspliceosome. Because most alternatively spliced mRNA isoforms vary between different cell and tissue types, the ability to perform alternative splicing is expected to be an integral part of the supraspliceosome, which constitutes the splicing machine in vivo. Here we show that both the constitutively and alternatively spliced mRNAs of the endogenous human pol II transcripts: hnRNP A/B, survival of motor neuron (SMN) and ADAR2 are predominantly found in supraspliceosomes. This finding is consistent with our observations that the splicing regulators hnRNP G as well as all phosphorylated SR proteins are predominantly associated with supraspliceosomes. We further show that changes in alternative splicing of hnRNP A/B, affected by up regulation of SRSF5 (SRp40) or by treatment with C6-ceramide, occur within supraspliceosomes. These observations support the proposed role of the supraspliceosome in splicing regulation and alternative splicing.
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