UPF1/SMG7-dependent microRNA-mediated gene regulation

Jungyun Park, Jwa-Won Seo, Narae Ahn, Seokju Park, Jungwook Hwang () and Jin-Wu Nam ()
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Jungyun Park: Hanyang University
Jwa-Won Seo: Hanyang University
Narae Ahn: Hanyang University
Seokju Park: Hanyang University
Jungwook Hwang: Hanyang University
Jin-Wu Nam: Hanyang University

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12123-7

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