This study reveals that long noncoding RNAs (lncRNAs) can transactivate Staufen1 (STAU1)-mediated mRNA decay (SMD) by forming duplexes with 3'UTRs of target mRNAs through Alu elements. STAU1 binds to double-stranded (ds)RNA in the 3'UTR of mRNAs to promote their decay. Previously, the STAU1 binding site (SBS) in ARF1 mRNA was identified as a 19-base-pair stem with a 100-nucleotide apex. However, similar structures were not found in other SMD targets. The study found that SBSs 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 lncRNA. These lncRNAs, termed "half(!)-sbsRNAs," can downregulate subsets of SMD targets, and distinct lncRNAs can downregulate the same target. The study identified that 3'UTR Alu elements are enriched in SMD targets compared to the bulk of cellular mRNAs. Alu elements, the most abundant repeats in the human genome, are known to influence gene expression. The study suggests that imperfect base-pairing between Alu elements in lncRNAs and mRNAs can create SBSs, which are stabilized by STAU1. This mechanism allows lncRNAs to recruit STAU1 to mRNAs and mediate their decay. The study also found that STAU1 siRNA and half(!)-sbsRNA1 siRNA both increase the levels of SERPINE1 and FLJ21870 mRNAs, indicating that the reduction in mRNA abundance is due to SMD. The study further demonstrated that half(!)-sbsRNA1 can co-immunoprecipitate with STAU1 and specific SMD targets, confirming the formation of SBSs. The presence of UPF1 in the co-immunoprecipitation complex supports the idea that STAU1 bound to an SBS interacts with UPF1. The study also showed that downregulating STAU1 or UPF1 increases the abundance of SMD targets, indicating that these proteins are involved in the decay process. The findings suggest that lncRNAs can function as trans-acting RNA effectors by forming SBSs with mRNAs, which is a novel mechanism for regulating mRNA decay. The study highlights the potential complexity of regulatory networks involving lncRNA-mRNA duplexes and their role in gene expression. The results provide new insights into the mechanisms of SMD and the role of lncRNAs in mRNA regulation.This study reveals that long noncoding RNAs (lncRNAs) can transactivate Staufen1 (STAU1)-mediated mRNA decay (SMD) by forming duplexes with 3'UTRs of target mRNAs through Alu elements. STAU1 binds to double-stranded (ds)RNA in the 3'UTR of mRNAs to promote their decay. Previously, the STAU1 binding site (SBS) in ARF1 mRNA was identified as a 19-base-pair stem with a 100-nucleotide apex. However, similar structures were not found in other SMD targets. The study found that SBSs 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 lncRNA. These lncRNAs, termed "half(!)-sbsRNAs," can downregulate subsets of SMD targets, and distinct lncRNAs can downregulate the same target. The study identified that 3'UTR Alu elements are enriched in SMD targets compared to the bulk of cellular mRNAs. Alu elements, the most abundant repeats in the human genome, are known to influence gene expression. The study suggests that imperfect base-pairing between Alu elements in lncRNAs and mRNAs can create SBSs, which are stabilized by STAU1. This mechanism allows lncRNAs to recruit STAU1 to mRNAs and mediate their decay. The study also found that STAU1 siRNA and half(!)-sbsRNA1 siRNA both increase the levels of SERPINE1 and FLJ21870 mRNAs, indicating that the reduction in mRNA abundance is due to SMD. The study further demonstrated that half(!)-sbsRNA1 can co-immunoprecipitate with STAU1 and specific SMD targets, confirming the formation of SBSs. The presence of UPF1 in the co-immunoprecipitation complex supports the idea that STAU1 bound to an SBS interacts with UPF1. The study also showed that downregulating STAU1 or UPF1 increases the abundance of SMD targets, indicating that these proteins are involved in the decay process. The findings suggest that lncRNAs can function as trans-acting RNA effectors by forming SBSs with mRNAs, which is a novel mechanism for regulating mRNA decay. The study highlights the potential complexity of regulatory networks involving lncRNA-mRNA duplexes and their role in gene expression. The results provide new insights into the mechanisms of SMD and the role of lncRNAs in mRNA regulation.