This study investigates the role of long noncoding RNAs (lncRNAs) in the Staufen1 (STAU1)-mediated mRNA decay (SMD) pathway. The authors found that lncRNAs can form duplexes with Alu elements within the 3'UTRs of target mRNAs, creating half-STAU1 binding sites (½-SBSs). These ½-SBSs recruit STAU1 and its partner Upf1 to target mRNAs, leading to their decay. The study identified specific lncRNAs, such as lncRNA_AF087999 (½-sbsRNA1), that target SERPINE1 and FLJ21870 mRNAs for SMD. The formation of these duplexes is stabilized by STAU1, and the level of STAU1 does not affect the stability of ½-sbsRNA1. The study also demonstrated that ½-sbsRNA1 co-immunoprecipitates with STAU1 and is required for STAU1 binding to specific SMD targets. Additionally, other lncRNAs containing Alu elements were found to target specific mRNAs for SMD, highlighting the complex regulatory network involving lncRNA-mRNA duplexes and STAU1. This work reveals a novel mechanism by which lncRNAs can modulate mRNA decay through intermolecular base-pairing with Alu elements in the 3'UTRs of target mRNAs.This study investigates the role of long noncoding RNAs (lncRNAs) in the Staufen1 (STAU1)-mediated mRNA decay (SMD) pathway. The authors found that lncRNAs can form duplexes with Alu elements within the 3'UTRs of target mRNAs, creating half-STAU1 binding sites (½-SBSs). These ½-SBSs recruit STAU1 and its partner Upf1 to target mRNAs, leading to their decay. The study identified specific lncRNAs, such as lncRNA_AF087999 (½-sbsRNA1), that target SERPINE1 and FLJ21870 mRNAs for SMD. The formation of these duplexes is stabilized by STAU1, and the level of STAU1 does not affect the stability of ½-sbsRNA1. The study also demonstrated that ½-sbsRNA1 co-immunoprecipitates with STAU1 and is required for STAU1 binding to specific SMD targets. Additionally, other lncRNAs containing Alu elements were found to target specific mRNAs for SMD, highlighting the complex regulatory network involving lncRNA-mRNA duplexes and STAU1. This work reveals a novel mechanism by which lncRNAs can modulate mRNA decay through intermolecular base-pairing with Alu elements in the 3'UTRs of target mRNAs.