Addressing mRNAs to the ER: cis sequences act up!

Translation-coupled protein translocation requires that mRNAs encoding secreted and membrane proteins (mSMPs) reach the ER membrane. The classical view is that the signal recognition particle (SRP) pathway delivers translating signal sequence-containing proteins to the SRP receptor present on the ER surface and engages the translocation machinery. However, recent studies demonstrate both SRP- and translation-independent mRNA recruitment to the ER, and that mRNAs encoding non-signal sequence-containing cytosolic proteins (mCPs) might be full-time residents of ER membranes. Furthermore, translation-independent cis-acting sequence elements present in both mCPs and mSMPs appear to govern the ability of mRNAs to associate with ER. Thus, a more complex picture of how and why mRNAs target the ER is emerging.