mRNA encoding Sec61β, a tail-anchored protein, is localized on the endoplasmic reticulum

Abstract

While one pathway for the post-translational targeting of tail-anchored (TA) proteins to the endoplasmic reticulum (ER) has been well defined, it is unclear whether additional pathways exist. Here we provide evidence that a subset of mRNAs encoding TA-proteins, such as Sec61β and Nesprin2, is partially localized to the surface of the ER in mammalian cells. In particular, Sec61β mRNA can be targeted to, and later maintained on the ER using both translation-dependent and independent mechanisms. Our data suggests that this process is independent of p180, a known mRNA receptor on the ER, and the TRC/Get pathway components, TRC40 and BAT3. In addition, our data indicates that Sec61β mRNA may access translocon-bound ribosomes. Our results show that certain TA-proteins are likely synthesized directly on the ER, and this facilitates their membrane insertion. Thus it is clear that mammalian cells utilize multiple mechanisms to ensure efficient targeting of TA-proteins to the surface of the ER.