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lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements


Staufen 1 (STAU1)-mediated messenger RNA decay (SMD) involves the degradation of translationally active mRNAs whose 3′-untranslated regions (3′ UTRs) bind to STAU1, a protein that binds to double-stranded RNA1,2. Earlier studies defined the STAU1-binding site within ADP-ribosylation factor 1 (ARF1) mRNA as a 19-base-pair stem with a 100-nucleotide apex2. However, we were unable to identify comparable structures in the 3′ UTRs of other targets of SMD. Here we show that STAU1-binding sites can be formed by imperfect base-pairing between an Alu element in the 3′ UTR of an SMD target and another Alu element in a cytoplasmic, polyadenylated long non-coding RNA (lncRNA). An individual lncRNA can downregulate a subset of SMD targets, and distinct lncRNAs can downregulate the same SMD target. These are previously unappreciated functions of non-coding RNAs and Alu elements3,4,5. Not all mRNAs that contain an Alu element in the 3′ UTR are targeted for SMD even in the presence of a complementary lncRNA that targets other mRNAs for SMD. Most known trans-acting RNA effectors consist of fewer than 200 nucleotides, and these include small nucleolar RNAs and microRNAs. Our finding that the binding of STAU1 to mRNAs can be transactivated by lncRNAs uncovers an unexpected strategy that cells use to recruit proteins to mRNAs and mediate the decay of these mRNAs. We name these lncRNAs half-STAU1-binding site RNAs (1/2-sbsRNAs).

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Figure 1: 1/2-sbsRNA1 binds to, and reduces the abundance of, specific SMD targets.
Figure 2: 1/2-sbsRNA1 co-immunoprecipitates with STAU1 and is required for STAU1 binding to specific SMD targets.
Figure 3: Evidence that 1/2-sbsRNA2, 1/2-sbsRNA3 and 1/2-sbsRNA4 base-pair with particular mRNA 3′ UTRs and decrease mRNA abundance, as do STAU1 and UPF1.

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  1. Gong, C., Kim, Y. K., Woeller, C. F., Tang, Y. & Maquat, L. E. SMD and NMD are competitive pathways that contribute to myogenesis: effects on PAX3 and myogenin mRNAs. Genes Dev. 23, 54–66 (2009)

    Article  CAS  Google Scholar 

  2. Kim, Y. K. et al. Staufen1 regulates diverse classes of mammalian transcripts. EMBO J. 26, 2670–2681 (2007)

    Article  CAS  Google Scholar 

  3. Cordaux, R. & Batzer, M. A. The impact of retrotransposons on human genome evolution. Nature Rev. Genet. 10, 691–703 (2009)

    Article  CAS  Google Scholar 

  4. Wilusz, J. E., Sunwoo, H. & Spector, D. L. Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 23, 1494–1504 (2009)

    Article  CAS  Google Scholar 

  5. Walters, R. D., Kugel, J. F. & Goodrich, J. A. InvAluable junk: the cellular impact and function of Alu and B2 RNAs. IUBMB Life 61, 831–837 (2009)

    Article  CAS  Google Scholar 

  6. Zuker, M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 31, 3406–3415 (2003)

    Article  CAS  Google Scholar 

  7. Yulug, I. G., Yulug, A. & Fisher, E. M. The frequency and position of Alu repeats in cDNAs, as determined by database searching. Genomics 27, 544–548 (1995)

    Article  CAS  Google Scholar 

  8. Batzer, M. A. & Deininger, P. L. Alu repeats and human genomic diversity. Nature Rev. Genet. 3, 370–379 (2002)

    Article  CAS  Google Scholar 

  9. Hasler, J. & Strub, K. Alu elements as regulators of gene expression. Nucleic Acids Res. 34, 5491–5497 (2006)

    Article  Google Scholar 

  10. Chen, L. L., DeCerbo, J. N. & Carmichael, G. G. Alu element-mediated gene silencing. EMBO J. 27, 1694–1705 (2008)

    Article  CAS  Google Scholar 

  11. Pang, K. C. et al. RNAdb 2.0—an expanded database of mammalian non-coding RNAs. Nucleic Acids Res. 35, D178–D182 (2007)

    Article  CAS  Google Scholar 

  12. Engström, P. G. et al. Complex loci in human and mouse genomes. PLoS Genet. 2, e47 (2006)

    Article  Google Scholar 

  13. Kim, Y. K., Furic, L., Desgroseillers, L. & Maquat, L. E. Mammalian Staufen1 recruits Upf1 to specific mRNA 3′UTRs so as to elicit mRNA decay. Cell 120, 195–208 (2005)

    Article  CAS  Google Scholar 

  14. Kim, H. H. et al. HuR recruits let-7/RISC to repress c-Myc expression. Genes Dev. 23, 1743–1748 (2009)

    Article  CAS  Google Scholar 

  15. Kuwano, Y. et al. NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif. Nucleic Acids Res. 38, 225–238 (2010)

    Article  CAS  Google Scholar 

  16. Ashley, C. T., Jr, Wilkinson, K. D., Reines, D. & Warren, S. T. FMR1 protein: conserved RNP family domains and selective RNA binding. Science 262, 563–566 (1993)

    Article  ADS  CAS  Google Scholar 

  17. Bartel, D. P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215–233 (2009)

    Article  CAS  Google Scholar 

  18. Kapranov, P., Willingham, A. T. & Gingeras, T. R. Genome-wide transcription and the implications for genomic organization. Nature Rev. Genet. 8, 413–423 (2007)

    Article  CAS  Google Scholar 

  19. Mathews, D. H., Sabina, J., Zuker, M. & Turner, D. H. Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J. Mol. Biol. 288, 911–940 (1999)

    Article  CAS  Google Scholar 

  20. Xia, T. et al. Thermodynamic parameters for an expanded nearest-neighbor model for formation of RNA duplexes with Watson–Crick base pairs. Biochemistry 37, 14719–14735 (1998)

    Article  CAS  Google Scholar 

  21. Liang, C. C., Park, A. Y. & Guan, J. L. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro . Nature Protocols 2, 329–333 (2007)

    Article  CAS  Google Scholar 

  22. Providence, K. M. et al. SERPINE1 (PAI-1) is deposited into keratinocyte migration ‘trails’ and required for optimal monolayer wound repair. Arch. Dermatol. Res. 300, 303–310 (2008)

    Article  CAS  Google Scholar 

  23. Marion, R. M., Fortes, P., Beloso, A., Dotti, C. & Ortin, J. A human sequence homologue of Staufen is an RNA-binding protein that is associated with polysomes and localizes to the rough endoplasmic reticulum. Mol. Cell. Biol. 19, 2212–2219 (1999)

    Article  CAS  Google Scholar 

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We thank D. Mathews and A. Grossfield for the use of computer clusters, D. Matthews for access to the program Structure 5.0, K. Nerhrke for fluorescence microscope time, S. de Lucas and J. Ortíz for anti-STAU1 antibodies, M. Gorospe for pcDNA3-MS2bsX12, S. Higgins and P. Higgins for HaCaT cells and advice on the scrape-injury repair assay, J. Wang for the initial BAG5 mRNA assays, and O. Isken, M. Gleghorn and D. Matthews for comments on the manuscript. This work was supported by the National Institutes of Health (GM074593 to L.E.M.) and an Elon Huntington Hooker Graduate Student Fellowship (C.G.).

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C.G. wrote the Perl programs and performed the bioinformatics analyses and wet-bench experiments. C.G. and L.E.M. analysed the computational data, designed the wet-bench experiments, analysed the resultant data and wrote the manuscript.

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Correspondence to Lynne E. Maquat.

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The authors declare no competing financial interests.

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Gong, C., Maquat, L. lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements. Nature 470, 284–288 (2011).

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