The ribosome-engaged landscape of alternative splicing.
The ribosome-engaged landscape of alternative splicing.
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DOI：
10.1038/nsmb.3317
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发表时间：
2016-12
影响因子：
16.8
通讯作者：
Blencowe BJ
中科院分区：
文献类型：
--
作者：
Weatheritt RJ;Sterne-Weiler T;Blencowe BJ
高通量RNA测序（RNA-Seq）揭示了不同细胞和组织类型中可变剪接（AS）的巨大复杂性。然而，目前还不知道剪接变体转录物的库在多大程度上被翻译成蛋白质产物。在这里，我们调查的核糖体从事的AS事件。值得注意的是，使用RNA-Seq数据在中高丰度转录物中检测到的至少75%的人外显子跳跃事件也在核糖体分析数据中检测到。此外，功能相关的剪接变异体的相对较小的子集从事核糖体的水平，不反映其绝对丰度，表明AS在调节翻译输出的重要作用。我们表明，这种模式的调节与哺乳动物细胞周期的控制。因此，我们的研究结果表明，剪接变异体的主要部分是翻译，和特定的细胞功能，包括细胞周期的控制受到AS依赖性调制的翻译输出。
High-throughput RNA-sequencing (RNA-Seq) has revealed an enormous complexity of alternative splicing (AS) across diverse cell and tissue types. However, it is currently not known to what extent repertoires of splice variant transcripts are translated into protein products. Here, we survey AS events engaged by the ribosome. Remarkably, at least 75% of human exon skipping events detected in medium to high abundance transcripts using RNA-Seq data are also detected in ribosome profiling data. Furthermore, relatively small subsets of functionally related splice variants are engaged by ribosomes at levels that do not reflect their absolute abundance, indicating an important role for AS in modulating translational output. We show that this mode of regulation is associated with control of the mammalian cell cycle. Our results thus suggest that a major fraction of splice variants is translated, and that specific cellular functions including cell cycle control are subject to AS-dependent modulation of translation output.