The Zavolan lab in collaboration with the Spang lab and the NCCR Cryo-EM platform, investigated the expression,  structure within the ribosome and function of the ribosomal protein paralog 39L (RPL39L). They could detect RPL39L expression in other cells and tissues e.g. cancer cell lines in addition to mouse germ cells. In mouse embryonic stem cells, they could show that a knockout of the protein affects translational dynamics involved in determinig the celllular differentiation state. Structural experiments revealed that RPL39L opposite to RPL39L has two conformations when bound to the ribosome leading to a hydrophobic patch which is thought to help co-translational folding of alpha helices. In conclusion, they could show how a ribosome paralog protein is used by cells to adapt translation to the requirements of different cell types. Their publication "Ribosomal protein RPL39L is an efficiency factor in the cotranslational folding of a subset of proteins with alpha helical domains" has been published in Nucleic Acids Research.

Abstract
Increasingly many studies reveal how ribosome composition can be tuned to optimally translate the transcriptome of individual cell types. In this study, we investigated the expression pattern, structure within the ribosome and effect on protein synthesis of the ribosomal protein paralog 39L (RPL39L). With a novel mass spectrometric approach we revealed the expression of RPL39L protein beyond mouse germ cells, in human pluripotent cells, cancer cell lines and tissue samples. We generated RPL39L knock-out mouse embryonic stem cell (mESC) lines and demonstrated that RPL39L impacts the dynamics of translation, to support the pluripotency and differentiation, spontaneous and along the germ cell lineage. Most differences in protein abundance between WT and RPL39L KO lines were explained by widespread autophagy. By CryoEM analysis of purified RPL39 and RPL39L-containing ribosomes we found that, unlike RPL39, RPL39L has two distinct conformations in the exposed segment of the nascent peptide exit tunnel, creating a distinct hydrophobic patch that has been predicted to support the efficient co-translational folding of alpha helices. Our study shows that ribosomal protein paralogs provide switchable modular components that can tune translation to the protein production needs of individual cell types.

Read the Publication in Nucleic Acids Research (Open Access)

Website Zavolan Lab
Website Spang Lab
Website ETH Cryo-EM Knowledge Hub

Abstract and figure from Banerjee, Ataman, Smialek et al (2024) Nucleic Acids Res published under a CC BY 4.0 license.