Primary Role for Endoplasmic Reticulum-bound Ribosomes in Cellular Translation Identified by Ribosome Profiling

• Published in: The Journal of biological chemistry Vol. 287; no. 8; pp. 5518 - 5527
• Main Authors: Reid, David W., Nicchitta, Christopher V.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.02.2012; American Society for Biochemistry and Molecular Biology
• Subjects: Cytosol - metabolism; Endoplasmic Reticulum (ER); Endoplasmic Reticulum - genetics; Endoplasmic Reticulum - metabolism; Genomics; HEK293 Cells; Humans; mRNA; Polyribosomes - genetics; Polyribosomes - metabolism; Protein Biosynthesis; Protein Synthesis; Protein Synthesis and Degradation; Ribosomes; Ribosomes - genetics; Ribosomes - metabolism; RNA, Messenger - genetics; Signal Recognition Particle; Trafficking; mRNA; Protein Synthesis; Signal Recognition Particle; Trafficking; Ribosomes; Endoplasmic Reticulum (ER)
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111.312280

In eukaryotic cells, the spatial regulation of protein expression is frequently conferred through the coupling of mRNA localization and the local control of translation. mRNA localization to the endoplasmic reticulum (ER) is a prominent example of such regulation and serves a ubiquitous role in segregating the synthesis of secretory and integral membrane proteins to the ER. Recent genomic and biochemical studies have now expanded this view to suggest a more substantial role for the ER cellular protein synthesis. We have utilized cell fractionation and ribosome profiling to obtain a genomic survey of the subcellular organization of mRNA translation and report that ribosomal loading of mRNAs, a proxy for mRNA translation, is biased to the ER. Notably, ER-associated mRNAs encoding both cytosolic and topogenic signal-encoding proteins display similar ribosome loading densities, suggesting that ER-associated ribosomes serve a global role in mRNA translation. We propose that the partitioning of mRNAs and their translation between the cytosol and ER compartments may represent a novel mechanism for the post-transcriptional regulation of gene expression. mRNA translation is compartmentalized between cytosolic and ER-bound ribosomes. Genomic ribosome profiling demonstrates that the mRNA transcriptome is preferentially translated on ER membrane-bound ribosomes. The endoplasmic reticulum serves a global role in mRNA transcriptome expression. Partitioning of mRNAs between the cytosol and endoplasmic reticulum may represent a novel means of post-transcriptional gene regulation.