The landscape of alternative polyadenylation in single cells of the developing mouse embryo

Vikram Agarwal (), Sereno Lopez-Darwin, David R. Kelley and Jay Shendure ()
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Vikram Agarwal: Calico Life Sciences
Sereno Lopez-Darwin: University of Washington
David R. Kelley: Calico Life Sciences
Jay Shendure: University of Washington

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-25388-8

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