The landscape of alternative polyadenylation in single cells of the developing mouse embryo.
The landscape of alternative polyadenylation in single cells of the developing mouse embryo.
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DOI：
10.1038/s41467-021-25388-8
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发表时间：
2021-08-24
影响因子：
16.6
通讯作者：
Shendure J
中科院分区：
文献类型：
--
作者：
Agarwal V;Lopez-Darwin S;Kelley DR;Shendure J
3′非翻译区（3′ UTR）在转录后调节mRNA的稳定性、定位和翻译速率。虽然3′-UTR异构体已经在有限的细胞类型中使用批量测量进行了全面定量，但在哺乳动物发育期间，它们在细胞类型中的差异使用仍然很难表征。在这项研究中，我们检查了一个数据集，包括跨越E9.5-E13.5小鼠胚胎发育的约200万个细胞核，以量化替代性多聚腺苷酸化（阿帕）的全转录组变化。我们观察到所有细胞类型的3 'UTR在整个胚胎阶段均整体延长，尽管我们在每个阶段的造血谱系中检测到较短的3' UTR，而在神经元细胞类型中检测到较长的3 'UTR。RNA结合蛋白（RBP）动力学分析鉴定了ELAV样家族成员，这些成员在经历3′-UTR延长的神经元谱系和发育阶段中伴随诱导，作为阿帕的假定调节因子。通过测量3′-UTR异构体在一个庞大的单细胞数据集，我们的工作提供了一个转录组范围和生物体范围的地图，在哺乳动物器官发生过程中的替代聚腺苷酸化的动态景观。选择性多聚腺苷酸化调节mRNA亚型的定位、半衰期和翻译。在这里，作者使用来自小鼠胚胎的单细胞RNA测序数据研究了替代的多聚腺苷酸化，并鉴定了在细胞类型和发育时间中受到调控的3 '-UTR亚型。
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 examine a dataset comprising ~2 million nuclei 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 RNA-binding protein (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. Alternative polyadenylation regulates localization, half-life and translation of mRNA isoforms. Here the authors investigate alternative polyadenylation using single cell RNA sequencing data from mouse embryos and identify 3’-UTR isoforms that are regulated across cell types and developmental time.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
4.6
作者：
Fontes MM;Guvenek A;Kawaguchi R;Zheng D;Huang A;Ho VM;Chen PB;Liu X;O'Dell TJ;Coppola G;Tian B;Martin KC
通讯作者：
Martin KC
影响因子：
12.3
作者：
Agarwal V;Subtelny AO;Thiru P;Ulitsky I;Bartel DP
通讯作者：
Bartel DP
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
影响因子：
8.8
作者：
Agarwal, Vikram;Shendure, Jay
通讯作者：
Shendure, Jay