Total RNA sequencing reveals nascent transcription and widespread co-transcriptional splicing in the human brain

Total RNA sequencing reveals nascent transcription and widespread co-transcriptional splicing in the human brain
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DOI:
10.1038/nsmb.2143
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发表时间:
2011-12-01
影响因子:
16.8
通讯作者:
Feuk, Lars
Feuk, Lars
中科院分区:
生物学1区
文献类型:
--
作者:
Ameur, Adam;Zaghlool, Ammar;Feuk, Lars

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转录组测序能够以碱基对分辨率对成熟RNA进行分析。在此我们表明,RNA - seq也可用于研究正在转录的新生RNA。我们对人脑和肝脏的总RNA进行了测序,发现在内含子中有很大一部分读段(高达40%)。内含子RNA在脑组织中含量丰富,特别是对于涉及轴突生长和突触传递的基因。此外,我们检测到胎儿脑和成人脑之间内含子RNA水平存在显著差异。我们表明,内含子序列读段覆盖模式可以通过新生转录与共转录剪接相结合来解释。对共转录剪接的进一步分析表明,缓慢去除的内含子与可变剪接之间存在相关性。我们的数据表明,总RNA测序为细胞中的转录过程提供了独特的见解,对正常脑发育具有特别重要的意义。
Transcriptome sequencing allows for analysis of mature RNAs at base pair resolution. Here we show that RNA-seq can also be used for studying nascent RNAs undergoing transcription. We sequenced total RNA from human brain and liver and found a large fraction of reads (up to 40%) within introns. Intronic RNAs were abundant in brain tissue, particularly for genes involved in axonal growth and synaptic transmission. Moreover, we detected significant differences in intronic RNA levels between fetal and adult brains. We show that the pattern of intronic sequence read coverage is explained by nascent transcription in combination with co-transcriptional splicing. Further analysis of co-transcriptional splicing indicates a correlation between slowly removed introns and alternative splicing. Our data show that sequencing of total RNA provides unique insight into the transcriptional processes in the cell, with particular importance for normal brain development.