Abstract
We report a new mechanism by which human mRNAs cross-talk: an Alu element in the 3′ untranslated region (3′ UTR) of one mRNA can base-pair with a partially complementary Alu element in the 3′ UTR of a different mRNA, thereby creating a Staufen1 (STAU1)-binding site (SBS). STAU1 binding to a 3′-UTR SBS was previously shown to trigger STAU1-mediated mRNA decay (SMD) by directly recruiting the ATP-dependent RNA helicase UPF1, which is also a key factor in the mechanistically related nonsense-mediated mRNA decay (NMD) pathway. In the case of a 3′-UTR SBS created by mRNA-mRNA base-pairing, we show that SMD targets both mRNAs in the duplex, provided that both mRNAs are translated. If only one mRNA is translated, then it alone is targeted for SMD. We demonstrate the functional importance of mRNA–mRNA–triggered SMD in cell migration and invasion.
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Change history
04 December 2013
In the version of this article initially published, the last sentence of the Figure 5 legend reads: "Downregulation of SOWAHC mRNA inhibits SOWAHC mRNA-CDCP1 mRNA base-pairing and thus the SOWAHC mRNA-mediated SMD of CDCP1 mRNA, an mRNA that encodes a protein that inhibits cell migration and invasion." However, "a protein that inhibits" should have read "a protein that promotes." The error has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
We thank D. Mathews for computational advice, K. Nehrke for access to his inverted fluorescence microscope, S. de Lucas and J. Ortín (Centro Nacional de Biotecnología, Madrid, Spain) for anti-STAU1 antibody, C. Beckham for help with the trans-well assay and M.W.-L. Popp for comments on the manuscript. This work was supported by the US National Institutes of Health (GM074593 to L.E.M.) and a University of Rochester Messersmith Graduate Student Fellowship (C.G.).
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C.G. wrote the Perl programs and undertook the bioinformatics analyses and performed, with assistance from Y.T., wet-bench experiments. C.G. and L.E.M. designed the experiments, analyzed experimental data and wrote the manuscript.
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Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–6 (PDF 2693 kb)
Supplementary Table 1
△G of predicted duplexes formed between the 3′UTR Alu element of each specified ensembl transcript and the 3′UTR Alu element of each of three proven SMD targets (XLS 375 kb)
Supplementary Table 3
Length of 3′UTR and siRNA annealing site(s) for each analyzed mRNA (XLS 22 kb)
Supplementary Table 3
Primers used in RT-sqPCR or RT-qPCR (XLS 22 kb)
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Gong, C., Tang, Y. & Maquat, L. mRNA–mRNA duplexes that autoelicit Staufen1-mediated mRNA decay. Nat Struct Mol Biol 20, 1214–1220 (2013). https://doi.org/10.1038/nsmb.2664
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DOI: https://doi.org/10.1038/nsmb.2664
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