Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, USA.
Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, College of the Environment and Ecology, Xiamen University, Xiamen, China.
RNA Biol. 2021 Dec;18(12):2594-2604. doi: 10.1080/15476286.2021.1933732. Epub 2021 Jun 7.
Alternative polyadenylation (APA) is a widespread post-transcriptional modification method that changes the 3' ends of transcripts by altering poly(A) site usage. However, the longitudinal transcriptomic 3' end profile and its mechanism of action are poorly understood. We applied diurnal time-course poly(A) tag sequencing (PAT-seq) for and identified 3284 genes that generated both rhythmic and arrhythmic transcripts. These two classes of transcripts appear to exhibit dramatic differences in expression and translation activisty. The asynchronized transcripts derived by APA are embedded with different poly(A) signals, especially for rhythmic transcripts, which contain higher AAUAAA and UGUA signal proportions. The Pol II occupancy maximum is reached upstream of rhythmic poly(A) sites, while it is present directly at arrhythmic poly(A) sites. Integrating H3K9ac and H3K4me3 time-course data analyses revealed that transcriptional activation of histone markers may be involved in the differentiation of rhythmic and arrhythmic APA transcripts. These results implicate an interplay between histone modification and RNA 3'-end processing, shedding light on the mechanism of transcription rhythm and alternative polyadenylation.
可变多聚腺苷酸化(APA)是一种广泛存在的转录后修饰方法,通过改变多聚腺苷酸位点的使用来改变转录本的 3' 端。然而,长时程转录组 3' 端谱及其作用机制仍知之甚少。我们应用昼夜时间过程多聚腺苷酸化标签测序(PAT-seq)对 进行了研究,鉴定出了 3284 个产生节律性和非节律性转录本的基因。这两类转录本在表达和翻译活性方面似乎存在明显差异。通过 APA 产生的非同步转录本嵌入了不同的多聚腺苷酸信号,特别是对于节律性转录本,其包含更高比例的 AAUAAA 和 UGUA 信号。Pol II 占据最大值出现在节律性多聚腺苷酸位点的上游,而在非节律性多聚腺苷酸位点则直接存在。整合 H3K9ac 和 H3K4me3 时程数据分析表明,组蛋白标记物的转录激活可能参与了节律性和非节律性 APA 转录本的分化。这些结果表明组蛋白修饰和 RNA 3'-末端加工之间存在相互作用,为转录节律和可变多聚腺苷酸化的机制提供了线索。