Mammalian Staufen1 (Stau1) is a ubiquitous double-stranded RNA-binding protein associated with polysomes. Stau1 has two protein isoforms with molecular weights of 55 kDa and 63 kDa. The 55-kDa isoform associates with the 40S and 60S ribosomal subunits and colocalizes with the rough endoplasmic reticulum. Stau1 is thought to be involved in transporting mRNA and in controlling and eliciting mRNA decay. Previous studies have shown that Stau1 recruits upf1 to the 3′ untranslated region (3’UTR) of Arf1 mRNA and induces the Stau1-mediated mRNA decay (SMD). A recent study suggests that Stau1 regulates diverse classes of mammalian transcripts. In order to identify the mRNA targets of Staufen proteins, RIP-assay technology was employed and identified distinct but overlapping subsets of cellular mRNAs associated with Stau1- and Stau2-containing ribonucleoprotein complexes.