Single GAPDH mRNAs (green) localize to the ER (red) in detergent-extracted green African monkey cells.
The Palazzo lab, in collaboration with Jeff Chao’s lab at the Friedrich Miescher Institute for Biomedical Research in Basel Switzerland, has resolved a long standing puzzle in how cells use mRNAs to synthesize proteins as detailed in a paper published in the most recent issue of Cell Reports (Single-Molecule Quantification of Translation-Dependent Association of mRNAs with the Endoplasmic Reticulum, Cell Reports 2017, 21: 3740–3753).
Proteins can be divided into two types: those that stay within the cell’s cytoplasm, and those that need to cross a membrane. Previously, it was known that most mRNAs that encode proteins that must cross membranes were localized to the surface of the endoplasmic reticulum (ER), a large tubulated organelle found inside of all eukaryotic cells. In contrast, it remained unclear whether other mRNAs were also targeted to this organelle or excluded from it. By imaging single molecules of mRNAs in fixed and live cells, this new study reveals that a substantial fraction of mRNAs that encode non-membrane targeted proteins are also localized to the surface of the ER by the protein synthesis machinery. Moreover, ER-associated mRNAs were more efficiently translated into proteins then their non-ER counterparts. This study adds a new wrinkle to our basic understanding of how proteins are synthesized. It also opens the door to new questions: Why are these mRNAs targeted? Why is it that ER-associated mRNAs are more efficiently translated? Are cytosolic and ER-associated mRNAs differentially regulated? How does this affect over gene regulation?
