Length-dependent translation efficiency of ER-destined proteins
Gene expression resulting in the generation of new proteins is a fundamental process critical for every living organism. Particularly in eukaryotic cells, complex organization of the cell body requires fine-tuning of every step prior to de novo protein synthesis. To ensure proper localization, certain mRNAs possess unique signal sequence, which destinies the translation apparatus to the specific organelle. Here we focus on the mechanisms governing the translation of signal sequence-bearing mRNAs, which encode proteins targeted to the endoplasmic reticulum (ER). The binding of a signal-recognition particle (SRP) to the translation machinery halts protein synthesis until the mRNA-ribosome complex reaches ER membrane. The commonly accepted model suggests that mRNA containing the ER signal peptide continuously repeats the cycle of SRP binding followed by association and dissociation with ER. In contrast with the current view, we show that the long mRNAs remain on the ER while being translated. On the other hand, due to a low ribosome occupancy, the short mRNAs continue the cycle always facing the translation pause. Ultimately, this leads to a significant drop in the translation efficiency of small, ER-targeted proteins. The proposed mechanism advances our understanding of selective protein synthesis in eukaryotic cells and provides new avenues to enhance protein production in biotechnological settings.