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

Author

Listed:
  • Vikram Agarwal

    (Calico Life Sciences)

  • Sereno Lopez-Darwin

    (University of Washington)

  • David R. Kelley

    (Calico Life Sciences)

  • Jay Shendure

    (University of Washington
    Howard Hughes Medical Institute
    Brotman Baty Institute for Precision Medicine, University of Washington
    Allen Discovery Center for Cell Lineage Tracing)

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.

Suggested Citation

  • Vikram Agarwal & Sereno Lopez-Darwin & David R. Kelley & Jay Shendure, 2021. "The landscape of alternative polyadenylation in single cells of the developing mouse embryo," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25388-8
    DOI: 10.1038/s41467-021-25388-8
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    Cited by:

    1. Austin M. Gabel & Andrea E. Belleville & James D. Thomas & Siegen A. McKellar & Taylor R. Nicholas & Toshihiro Banjo & Edie I. Crosse & Robert K. Bradley, 2024. "Multiplexed screening reveals how cancer-specific alternative polyadenylation shapes tumor growth in vivo," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Seungjae Lee & Yen-Chung Chen & Austin E. Gillen & J. Matthew Taliaferro & Bart Deplancke & Hongjie Li & Eric C. Lai, 2022. "Diverse cell-specific patterns of alternative polyadenylation in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Kenzui Taniue & Anzu Sugawara & Chao Zeng & Han Han & Xinyue Gao & Yuki Shimoura & Atsuko Nakanishi Ozeki & Rena Onoguchi-Mizutani & Masahide Seki & Yutaka Suzuki & Michiaki Hamada & Nobuyoshi Akimits, 2024. "The MTR4/hnRNPK complex surveils aberrant polyadenylated RNAs with multiple exons," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Valter Bergant & Daniel Schnepf & Niklas Andrade Krätzig & Philipp Hubel & Christian Urban & Thomas Engleitner & Ronald Dijkman & Bernhard Ryffel & Katja Steiger & Percy A. Knolle & Georg Kochs & Rola, 2023. "mRNA 3’UTR lengthening by alternative polyadenylation attenuates inflammatory responses and correlates with virulence of Influenza A virus," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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