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UPF1/SMG7-dependent microRNA-mediated gene regulation

Author

Listed:
  • Jungyun Park

    (Hanyang University)

  • Jwa-Won Seo

    (Hanyang University)

  • Narae Ahn

    (Hanyang University)

  • Seokju Park

    (Hanyang University)

  • Jungwook Hwang

    (Hanyang University
    Hanyang University)

  • Jin-Wu Nam

    (Hanyang University
    Hanyang University)

Abstract

The stability and quality of metazoan mRNAs are under microRNA (miRNA)-mediated and nonsense-mediated control. Although UPF1, a core mediator of nonsense-mediated mRNA decay (NMD), mediates the decay of target mRNA in a 3′UTR-length-dependent manner, the detailed mechanism remains unclear. Here, we suggest that 3′UTR-length-dependent mRNA decay is not mediated by nonsense mRNAs but rather by miRNAs that downregulate target mRNAs via Ago-associated UPF1/SMG7. Global analyses of mRNAs in response to UPF1 RNA interference in miRNA-deficient cells reveal that 3′UTR-length-dependent mRNA decay by UPF1 requires canonical miRNA targeting. The destabilization of miRNA targets is accomplished by the combination of Ago2 and UPF1/SMG7, which may recruit the CCR4-NOT deadenylase complex. Indeed, loss of the SMG7-deadenylase complex interaction increases the levels of transcripts regulated by UPF1-SMG7. This UPF1/SMG7-dependent miRNA-mediated mRNA decay pathway may enable miRNA targeting to become more predictable and expand the miRNA-mRNA regulatory network.

Suggested Citation

  • Jungyun Park & Jwa-Won Seo & Narae Ahn & Seokju Park & Jungwook Hwang & Jin-Wu Nam, 2019. "UPF1/SMG7-dependent microRNA-mediated gene regulation," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12123-7
    DOI: 10.1038/s41467-019-12123-7
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