bims-tricox 2023-10-29 papers

Issue of 2023–10–29
two papers selected by
Yash Verma, University of Zurich

J Mol Biol. 2023 Oct 19. pii: S0022-2836(23)00432-1. [Epub ahead of print] 168321

The role of ribosomal proteins eL15 and eL36 in the early steps of yeast 60S ribosomal subunit assembly.

José Fernández-Fernández, Sara Martín-Villanueva, Jorge Perez-Fernandez, Jesús de la Cruz.

Ribosomal proteins have important roles in maintaining the structure and function of mature ribosomes, but they also drive crucial rearrangement reactions during ribosome biogenesis. The contribution of most, but not all, ribosomal proteins to ribosome synthesis has been previously analyzed in the yeast Saccharomyces cerevisiae. Herein, we characterize the role of yeast eL15 during 60S ribosomal subunit formation. In vivo depletion of eL15 results in a shortage of 60S subunits and the appearance of half-mer polysomes. This is likely due to defective processing of the 27SA3 to the 27SBS pre-rRNA and impaired subsequent processing of both forms of 27SB pre-rRNAs to mature 25S and 5.8S rRNAs. Indeed, eL15 depletion leads to the efficient turnover of the de novo formed 27S pre-rRNAs. Additionally, depletion of eL15 blocks nucleocytoplasmic export of pre-60S particles. Moreover, we have analyzed the impact of depleting either eL15 or eL36 on the composition of early pre-60S particles, thereby revealing that the depletion of eL15 or eL36 not only affects each other's assembly into pre-60S particles but also that of neighboring ribosomal proteins, including eL8. These intermediates also lack most ribosome assembly factors required for 27SA3 and 27SB pre-rRNA processing, named A3- and B-factors, respectively. Importantly, our results recapitulate previous ones obtained upon eL8 depletion. We conclude that assembly of eL15, together with that of eL8 and eL36, is a prerequisite to shape domain I of 5.8S/25S rRNA within early pre-60S particles, through their binding to this rRNA domain and the recruitment of specific groups of assembly factors.

Keywords: Ribosome; eL8-eL15-eL36 ribosomal protein cluster; ribosomal RNA domain I; ribosome assembly; yeast

DOI: https://doi.org/10.1016/j.jmb.2023.168321

Cell Rep. 2023 Oct 25. pii: S2211-1247(23)01324-4. [Epub ahead of print]42(11): 113312

Mitochondrial gene expression is required for platelet function and blood clotting.

Tara R Richman, Judith A Ermer, Jessica Baker, Stefan J Siira, Benjamin T Kile, Matthew D Linden, Oliver Rackham, Aleksandra Filipovska.

Platelets are anucleate blood cells that contain mitochondria and regulate blood clotting in response to injury. Mitochondria contain their own gene expression machinery that relies on nuclear-encoded factors for the biogenesis of the oxidative phosphorylation system to produce energy required for thrombosis. The autonomy of the mitochondrial gene expression machinery from the nucleus is unclear, and platelets provide a valuable model to understand its importance in anucleate cells. Here, we conditionally delete Elac2, Ptcd1, or Mtif3 in platelets, which are essential for mitochondrial gene expression at the level of RNA processing, stability, or translation, respectively. Loss of ELAC2, PTCD1, or MTIF3 leads to increased megakaryocyte ploidy, elevated circulating levels of reticulated platelets, thrombocytopenia, and consequent extended bleeding time. Impaired mitochondrial gene expression reduces agonist-induced platelet activation. Transcriptomic and proteomic analyses show that mitochondrial gene expression is required for fibrinolysis, hemostasis, and blood coagulation in response to injury.

Keywords: CP: Immunology; megakaryocytes; mitochondria; mitochondrial gene expression; platelets; translation

DOI: https://doi.org/10.1016/j.celrep.2023.113312