Role of Rpl39l in translation, and consequences for pluripotency and cancer

Recent research increasingly demonstrates that ribosome composition can be adjusted to efficiently translate the transcriptome of specific cell types. In this study, we examined the expression pattern, structure within the ribosome, and the influence on protein synthesis of the ribosomal protein paralog RPL39L. Using a novel mass spectrometric technique, we discovered that RPL39L protein is expressed not only in mouse germ cells but also in human pluripotent cells, cancer cell lines, and tissue samples. We created RPL39L knock-out mouse embryonic stem cell (mESC) lines and found that RPL39L affects translation dynamics, supporting pluripotency and differentiation, both spontaneously and along the germ cell lineage. The differences in protein abundance between wild-type and RPL39L knockout lines were largely attributed to widespread autophagy. CryoEM analysis of purified ribosomes containing RPL39 and RPL39L revealed that, unlike RPL39, RPL39L adopts two distinct conformations in the exposed segment of the nascent peptide exit tunnel, forming a unique hydrophobic patch predicted to facilitate efficient co-translational folding of alpha helices. Our findings indicate that ribosomal protein paralogs serve as switchable modular components that can adapt translation to the specific protein production needs of different cell types.