Analysis of alternative cleavage and polyadenylation in mature and differentiating neurons using RNA-seq data
Analysis of alternative cleavage and polyadenylation in mature and differentiating neurons using RNA-seq data
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DOI：
10.1007/s40484-018-0148-3
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发表时间：
2018-09-01
影响因子：
3.1
通讯作者：
Tian, Bin
中科院分区：
文献类型：
--
作者：
Guvenek, Aysegul;Tian, Bin
背景大多数真核蛋白编码基因表现出选择性切割和多聚腺苷酸化 (APA)，从而产生具有不同 3 个非翻译区 (3 UTR) 的 mRNA 亚型。研究表明，脑细胞倾向于使用远端切割和聚腺苷酸化位点 (PAS) 来表达长 3 UTR 亚型。方法使用我们最近开发的综合 PAS 数据库 PolyA_DB，我们开发了一种有效的方法来检查 APA，称为使用 RNA-seq 的替代聚腺苷酸化的显着性分析 (SAAP-RS)。我们应用这种方法来研究脑细胞和神经发生中的APA。结果我们发现神经元整体表达比大脑中其他细胞类型更长的3'UTR，而小胶质细胞和内皮细胞表达明显更短的3'UTR。我们表明，脑细胞的 3' UTR 多样性可以通过单细胞测序数据得到证实。对胚胎干细胞分化为神经元过程中 3' UTR 的 APA 调节的进一步分析表明，在神经发生中调节的 APA 事件的很大一部分在肌发生中也受到类似的调节，但程度要大得多。 结论 总之，我们的数据描绘了不同脑细胞中的 APA 谱，并表明神经发生中的 APA 调节很大程度上是其他类型细胞分化中发生的增强过程。
BackgroundMost eukaryotic protein-coding genes exhibit alternative cleavage and polyadenylation (APA), resulting in mRNA isoforms with different 3 untranslated regions (3 UTRs). Studies have shown that brain cells tend to express long 3 UTR isoforms using distal cleavage and polyadenylation sites (PASs).MethodsUsing our recently developed, comprehensive PAS database PolyA_DB, we developed an efficient method to examine APA, named Significance Analysis of Alternative Polyadenylation using RNA-seq (SAAP-RS). We applied this method to study APA in brain cells and neurogenesis.ResultsWe found that neurons globally express longer 3 ' UTRs than other cell types in brain, and microglia and endothelial cells express substantially shorter 3 ' UTRs. We show that the 3 ' UTR diversity across brain cells can be corroborated with single cell sequencing data. Further analysis of APA regulation of 3 ' UTRs during differentiation of embryonic stem cells into neurons indicates that a large fraction of the APA events regulated in neurogenesis are similarly modulated in myogenesis, but to a much greater extent.ConclusionTogether, our data delineate APA profiles in different brain cells and indicate that APA regulation in neurogenesis is largely an augmented process taking place in other types of cell differentiation.