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U1 snRNP regulates cancer cell migration and invasion in vitro

Author

Listed:
  • Jung-Min Oh

    (University of Pennsylvania School of Medicine)

  • Christopher C. Venters

    (University of Pennsylvania School of Medicine)

  • Chao Di

    (University of Pennsylvania School of Medicine)

  • Anna Maria Pinto

    (University of Pennsylvania School of Medicine)

  • Lili Wan

    (University of Pennsylvania School of Medicine)

  • Ihab Younis

    (University of Pennsylvania School of Medicine)

  • Zhiqiang Cai

    (University of Pennsylvania School of Medicine)

  • Chie Arai

    (University of Pennsylvania School of Medicine)

  • Byung Ran So

    (University of Pennsylvania School of Medicine)

  • Jingqi Duan

    (University of Pennsylvania School of Medicine)

  • Gideon Dreyfuss

    (University of Pennsylvania School of Medicine)

Abstract

Stimulated cells and cancer cells have widespread shortening of mRNA 3’-untranslated regions (3’UTRs) and switches to shorter mRNA isoforms due to usage of more proximal polyadenylation signals (PASs) in introns and last exons. U1 snRNP (U1), vertebrates’ most abundant non-coding (spliceosomal) small nuclear RNA, silences proximal PASs and its inhibition with antisense morpholino oligonucleotides (U1 AMO) triggers widespread premature transcription termination and mRNA shortening. Here we show that low U1 AMO doses increase cancer cells’ migration and invasion in vitro by up to 500%, whereas U1 over-expression has the opposite effect. In addition to 3’UTR length, numerous transcriptome changes that could contribute to this phenotype are observed, including alternative splicing, and mRNA expression levels of proto-oncogenes and tumor suppressors. These findings reveal an unexpected role for U1 homeostasis (available U1 relative to transcription) in oncogenic and activated cell states, and suggest U1 as a potential target for their modulation.

Suggested Citation

  • Jung-Min Oh & Christopher C. Venters & Chao Di & Anna Maria Pinto & Lili Wan & Ihab Younis & Zhiqiang Cai & Chie Arai & Byung Ran So & Jingqi Duan & Gideon Dreyfuss, 2020. "U1 snRNP regulates cancer cell migration and invasion in vitro," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13993-7
    DOI: 10.1038/s41467-019-13993-7
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