Zhu Sheng, Wu Xiaohui, Fu Hongjuan, Ye Congting, Chen Moliang, Jiang Zhihua, Ji Guoli
Department of Automation, Xiamen University, Xiamen, China.
National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, China.
Front Genet. 2019 Jul 3;10:647. doi: 10.3389/fgene.2019.00647. eCollection 2019.
Alternative polyadenylation (APA) is an important post-transcriptional modification event to process messenger RNA (mRNA) for transcriptional termination, transport, and translation. In the present study, we characterized poly(A) signals in using 70,918 highly confident poly(A) sites derived from 16,511 protein-coding genes to understand their roles in the regulation of embryo development and gender difference. We examined potential factors, including the gene length, the number of introns in a gene, and the intron length, that may affect the prevalence of APA. We observed 12 prominent poly(A) signal patterns, which accounted for approximately 92% of total APA sites in . Among them, three patterns are specific to , so they are absent in other animals such as humans or mice. We catalogued APA sites based on their genomic regions and developed a bioinformatics pipeline to identify over-represented signal patterns for each class. Then the schema of elements for APA sites in each genomic region was proposed. More importantly, APA usage is dramatically dynamic in embryos along five developmental stages and well-coordinated with the maternal-to-zygotic transition event. We used an entropy-based method to identify developmental stage-specific APA sites and identified significant signal patterns around specific sites and constitutive sites. We found that the APA frequency in different genomic regions varies with developmental stages and that those sites located in intron or coding sequence regions contribute most to the dynamics of gene expression during developmental stages. This study deciphers the characteristics and poly(A) signal patterns for both canonical APA sites and non-canonical APA sites across different developmental stages and gender dimorphisms in , providing new insights into the dynamic regulation of distal and proximal APA.
可变聚腺苷酸化(APA)是一种重要的转录后修饰事件,用于处理信使核糖核酸(mRNA)以进行转录终止、运输和翻译。在本研究中,我们利用来自16511个蛋白质编码基因的70918个高度可靠的聚腺苷酸化位点,对[具体物种]中的聚腺苷酸化信号进行了表征,以了解它们在胚胎发育调控和性别差异中的作用。我们研究了可能影响APA发生率的潜在因素,包括基因长度、基因中的内含子数量和内含子长度。我们观察到12种显著的聚腺苷酸化信号模式,它们约占[具体物种]中APA位点总数的92%。其中,三种模式是[具体物种]特有的,因此在人类或小鼠等其他动物中不存在。我们根据基因组区域对APA位点进行了分类,并开发了一种生物信息学流程来识别每个类别中过度富集的信号模式。然后提出了每个基因组区域中APA位点的[具体物种]元件模式。更重要的是,在胚胎发育的五个阶段,APA的使用具有显著的动态变化,并且与母源-合子转变事件协调良好。我们使用基于熵的方法来识别发育阶段特异性的APA位点,并确定了特定位点和组成型位点周围的显著信号模式。我们发现不同基因组区域的APA频率随发育阶段而变化,并且位于内含子或编码序列区域的那些位点对发育阶段基因表达的动态变化贡献最大。这项研究破译了[具体物种]不同发育阶段和性别二态性中典型APA位点和非典型APA位点的特征及聚腺苷酸化信号模式,为远端和近端APA的动态调控提供了新的见解。