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Role of UPF1-LIN28A interaction during early differentiation of pluripotent stem cells

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  • Seungwon Jung

    (Hanyang University)

  • Seung Hwan Ko

    (Hanyang University)

  • Narae Ahn

    (Hanyang University)

  • Jinsam Lee

    (Hanyang University)

  • Chang-Hwan Park

    (Hanyang University)

  • Jungwook Hwang

    (Hanyang University
    Hanyang University)

Abstract

UPF1 and LIN28A are RNA-binding proteins involved in post-transcriptional regulation and stem cell differentiation. Most studies on UPF1 and LIN28A have focused on the molecular mechanisms of differentiated cells and stem cell differentiation, respectively. We reveal that LIN28A directly interacts with UPF1 before UPF1-UPF2 complexing, thereby reducing UPF1 phosphorylation and inhibiting nonsense-mediated mRNA decay (NMD). We identify the interacting domains of UPF1 and LIN28A; moreover, we develop a peptide that impairs UPF1-LIN28A interaction and augments NMD efficiency. Transcriptome analysis of human pluripotent stem cells (hPSCs) confirms that the levels of NMD targets are significantly regulated by both UPF1 and LIN28A. Inhibiting the UPF1-LIN28A interaction using a CPP-conjugated peptide promotes spontaneous differentiation by repressing the pluripotency of hPSCs during proliferation. Furthermore, the UPF1-LIN28A interaction specifically regulates transcripts involved in ectodermal differentiation. Our study reveals that transcriptome regulation via the UPF1-LIN28A interaction in hPSCs determines cell fate.

Suggested Citation

  • Seungwon Jung & Seung Hwan Ko & Narae Ahn & Jinsam Lee & Chang-Hwan Park & Jungwook Hwang, 2024. "Role of UPF1-LIN28A interaction during early differentiation of pluripotent stem cells," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44600-5
    DOI: 10.1038/s41467-023-44600-5
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    References listed on IDEAS

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    1. Manjeera Gowravaram & Juliane Schwarz & Sana K. Khilji & Henning Urlaub & Sutapa Chakrabarti, 2019. "Insights into the assembly and architecture of a Staufen-mediated mRNA decay (SMD)-competent mRNP," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    2. Brenda J. Reinhart & Frank J. Slack & Michael Basson & Amy E. Pasquinelli & Jill C. Bettinger & Ann E. Rougvie & H. Robert Horvitz & Gary Ruvkun, 2000. "The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans," Nature, Nature, vol. 403(6772), pages 901-906, February.
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