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Ribosomes, which synthesize the proteins of a cell, comprise ribosomal RNA and ribosomal proteins, which coassemble hierarchically during a process termed ribosome biogenesis. Historically, biochemical and molecular biology approaches have revealed how preribosomal particles form and mature in consecutive steps, starting in the nucleolus and terminating after nuclear export into the cytoplasm. However, only recently, due to the revolution in cryo–electron microscopy, could pseudoatomic structures of different preribosomal particles be obtained. Together with in vitro maturation assays, these findings shed light on how nascent ribosomes progress stepwise along a dynamic biogenesis pathway. Preribosomes assemble gradually, chaperoned by a myriad of assembly factors and small nucleolar RNAs, before they reach maturity and enter translation. This information will lead to a better understanding of how ribosome synthesis is linked to other cellular pathways in humans and how it can cause diseases, including cancer, if disturbed.
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Supplemental Video 1: The animation shows the successive folding and incorporation of the different 25S-5.8 rRNA domains during pre-60S biogenesis, as depicted in Figure 4. Supplemental Figures 1-2 (PDF). Supplemental Table 1: List of the assembly factors, rRNA molecules and ribosomal proteins present in the 90S and pre-40S particles, isolated from S. cerevisiae, C.thermophilum and H. sapiens, and which structures have been solved by cryo-EM. Indicated at the top are corresponding EMD and PDB ID numbers of the different particles, whereas the corresponding rows below contain the chain identifiers, which allows to find individual assembly factors, r-proteins or rRNAs in the corresponding PDB structures (XLSX). Supplemental Table 2: List of the assembly factors, rRNA molecules and ribosomal proteins present in the pre-60S particles isolated from S. cerevisiae, and in one case also reconstituted with the nuclear exosome for 7S rRNA processing, which structures have been solved by cryo-EM. Indicated at the top are corresponding EMD and PDB ID numbers of the different particles, whereas the corresponding rows below contain the chain identifiers, which allows to find individual assembly factors, r-proteins or rRNAs in the corresponding PDB structures (XLSX). Supplemental Table 3: List of different human diseases, known as ribosomopathies, caused by defects in ribosome assembly and function. The mutated factos underlying the individual disease given, together with the clinical phenotype. For further information, appropriate references are provided (PDF).