![]() ![]() A detailed knowledge of eukaryotic ribosome assembly is instrumental to eventually understand and treat ribosomopathies, diseases frequently caused by altered functionalities of ribosomal proteins.Ĭitation: Pillet B, García-Gómez JJ, Pausch P, Falquet L, Bange G, de la Cruz J, et al. Our findings emphasize that co-translational capturing of ribosomal proteins by dedicated chaperones is an advantageous strategy to provide sufficient amounts of assembly-competent ribosomal proteins. Notably, Acl4 has the capacity to recognize Rpl4 as it is synthesized by the ribosome. ![]() Here, we have identified such a dedicated chaperone, termed Acl4, which exclusively interacts with and accompanies the ribosomal protein Rpl4 to its nuclear assembly site. Recent evidence has highlighted that specific binding partners, referred to as dedicated chaperones, may ensure the soluble expression, nuclear import and/or correct assembly of ribosomal proteins. Many ribosomal proteins are prone to aggregation and need therefore to be protected on their path from the cytoplasm to their mostly nuclear incorporation sites within ribosome precursors. Actively growing yeast cells must produce more than 160’000 ribosomal proteins per minute in order to meet the cellular demand for new ribosomes. The biogenesis of eukaryotic ribosomes is an outstandingly complex process, in which around 80 ribosomal proteins and four ribosomal RNAs are accurately pieced together. Ribosomes are the molecular machines that generate proteins from mRNA templates. Taken together, our findings indicate that the dedicated chaperone Acl4 accompanies Rpl4 from the cytoplasm to its pre-60S assembly site in the nucleus. Notably, Acl4 localizes to both the cytoplasm and nucleus and it has the capacity to capture nascent Rpl4 in a co-translational manner. Genetic and biochemical evidence indicates that Acl4 can be considered as a dedicated chaperone of Rpl4. Absence of Acl4 confers a severe slow-growth phenotype and a deficiency in the production of 60S subunits. While Rpl4 contains at least five distinct nuclear localization signals (NLS), the C-terminal part of the long internal loop associates with a specific binding partner, termed Acl4. Here we show that both the long internal loop and the C-terminal eukaryote-specific extension are strictly required for the functionality of Rpl4. The 60S r-protein Rpl4 is particularly interesting since it harbours a conserved long internal loop and a prominent C-terminal eukaryote-specific extension. Many r-proteins contain universally conserved or eukaryote-specific internal loops and/or terminal extensions, which were shown to mediate their nuclear targeting and association with dedicated chaperones in a growing number of cases. Due to the high abundance and difficult physicochemical properties of r-proteins, their correct folding and fail-safe targeting to the assembly site depends largely on general, as well as highly specialized, chaperone and transport systems. Most r-proteins need to be transported from the cytoplasm to the nucleus where they get incorporated into the evolving pre-ribosomal particles. Yeast ribosomes are composed of four ribosomal RNAs (rRNAs) and 79 ribosomal proteins (r-proteins). The main principles underlying the making of ribosomes are conserved across eukaryotic organisms and this process has been studied in most detail in the yeast Saccharomyces cerevisiae. Ribosomes are the highly complex macromolecular assemblies dedicated to the synthesis of all cellular proteins from mRNA templates. ![]()
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