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The landscape of alternative polyadenylation in single cells of the developing mouse embryo
bioRxiv - Genomics Pub Date : 2021-03-24 , DOI: 10.1101/2021.01.21.427498
Vikram Agarwal , Sereno Lopez-Darwin , David R. Kelley , Jay Shendure

3' untranslated regions (3' UTRs) post-transcriptionally regulate mRNA stability, localization, and translation rate. While 3'-UTR isoforms have been globally quantified in limited cell types using bulk measurements, their differential usage among cell types during mammalian development remains poorly characterized. In this study, we examined a dataset comprising ~2 million cells spanning E9.5-E13.5 of mouse embryonic development to quantify transcriptome-wide changes in alternative polyadenylation (APA). We observe a global lengthening of 3' UTRs across embryonic stages in all cell types, although we detect shorter 3' UTRs in hematopoietic lineages and longer 3' UTRs in neuronal cell types within each stage. An analysis of RBP dynamics identifies ELAV-like family members, which are concomitantly induced in neuronal lineages and developmental stages experiencing 3'-UTR lengthening, as putative regulators of APA. By measuring 3'-UTR isoforms in an expansive single cell dataset, our work provides a transcriptome-wide and organism-wide map of the dynamic landscape of alternative polyadenylation during mammalian organogenesis.

中文翻译:

发育中的小鼠胚胎单细胞中替代性聚腺苷酸化的态势

转录后的3'非翻译区(3'UTR)调节mRNA的稳定性,定位和翻译速率。尽管已经使用大量测量方法在有限的细胞类型中对3'-UTR亚型进行了全局量化,但在哺乳动物发育过程中它们在细胞类型之间的差异用法仍然不明确。在这项研究中,我们检查了一个数据集,该数据集包含跨越小鼠胚胎发育的E9.5-E13.5的约200万个细胞,以量化备选聚腺苷酸化(APA)的转录组范围内的变化。尽管我们在每个阶段的造血谱系中检测到较短的3'UTR,而在每个阶段的神经元细胞类型中检测到较长的3'UTR,但在所有细胞类型中整个胚胎期的3'UTR都在全球范围内延长。对RBP动力学的分析确定了类似ELAV的家庭成员,作为APA的假定调节剂,它们在经历3'-UTR延长的神经元谱系和发育阶段中被同时诱导。通过在膨胀的单细胞数据集中测量3'-UTR同工型,我们的工作提供了在哺乳动物器官发生过程中备选多腺苷酸化动态态势的转录组范围和全生物范围的图谱。
更新日期:2021-03-25
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