Diversity and selectivity in mRNA translation on the endoplasmic reticulum

Key Points Ribosomes bound to the endoplasmic reticulum (ER) membrane translate a large and diverse population of mRNAs. Many mechanisms, including ribosome and mRNA binding, contribute to the recruitment of translation to the ER. Ribosomes and mRNAs associate with the ER over many successive rounds of protein synthesis. The ER and cytosol are distinct compartments for protein translation and post-transcriptional gene regulation. Localization of an mRNA can be an important regulatory variable during cell stress. Recent studies of mRNA distribution and translation show that, in addition to serving as the site of protein translocation into the endoplasmic reticulum (ER), ER-bound ribosomes translate a large fraction of mRNAs that encode cytosolic proteins. This, along with the discovery of many mechanisms for recruiting translation to the ER, suggests an expansive role for the ER in post-transcriptional gene expression. Pioneering electron microscopy studies defined two primary populations of ribosomes in eukaryotic cells: one freely dispersed through the cytoplasm and the other bound to the surface of the endoplasmic reticulum (ER). Subsequent investigations revealed a specialized function for each population, with secretory and integral membrane protein-encoding mRNAs translated on ER-bound ribosomes, and cytosolic protein synthesis was widely attributed to free ribosomes. Recent findings have challenged this view, and transcriptome-scale studies of mRNA distribution and translation have now demonstrated that ER-bound ribosomes also function in the translation of a large fraction of mRNAs that encode cytosolic proteins. These studies suggest a far more expansive role for the ER in transcriptome expression, where membrane and secretory protein synthesis represents one element of a multifaceted and dynamic contribution to post-transcriptional gene expression.