Mammalian Staufen is a double-stranded-RNA- and tubulin-binding protein which localizes to the rough endoplasmic reticulum

Staufen (Stau) is a double-stranded RNA (dsRNA)-binding protein involved in mRNA. transport and localization in Drosophila. To understand the molecula r mechanisms of mRNA transport in mammals, we cloned human (hStau) and mous e (mStau) staufen cDNAs. In humans, four transcripts arise by differential splicing of the Stau gene and code for two proteins with different N-termin al extremities. In vitro, hStau and mStau bind dsRNA via each of two full-l ength dsRNA-binding domains and tubulin via it region similar to the microt ubule-binding domain of MAP-1B, suggesting that Stau cross-links cytoskelet al and RNA components. Immunofluorescent double labeling of transfected mam malian cells revealed that Stau is localized to the rough endoplasmic retic ulum (RER), implicating this RNA-binding protein in mRNA targeting to the R ER, perhaps via a multistep process involving microtubules. These results a re the first demonstration of the association of an RNA-binding protein in addition to ribosomal proteins, with the RER, implicating this class of pro teins in the transport of RNA to its site of translation.