Staufen 1-mediated mRNA decay (SMD) is known to regulate the levels of transcripts involved in several cellular processes. SMD is triggered following binding of Staufen 1 to Staufen 1-binding sites (SBSs), which can form intramolecularly within an mRNA or through binding between an Alu element at the 3′ untranslated region (UTR) of an mRNA and a partially complementary Alu element of a long non-coding RNA. Here, the authors show that two mRNAs can also base-pair through their partially complementary 3′ UTR Alu elements, forming SBSs in the process. The mRNAs are then targeted for SMD, provided that they are translated and that the termination codon is sufficiently upstream of the SBS. Such SMD has functionally important consequences in cell migration and invasion.