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It has long been assumed that ribosomes do not show favoritism toward translating certain mRNAs. After all, eukaryotic messages can be translated even by E. coli ribosomes, and ribosomes from immature red blood cells have long been used to translate mRNAs from any source. However, evidence has shown that ribosomal proteins are not the same in all cells and that some ribosomal proteins are necessary for translating certain messages. When Kondrashov and colleagues (2011) mapped the gene that causes numerous axial skeleton deformities in mice, they found that the mutation was not in one of the well-known genes that control skeletal polarity. Rather, it was in ribosomal protein Rpl38. When this protein is mutated, the ribosomes can still translate most messages, but the ribosomes in the skeletal precursors cannot translate the mRNA from a specific subset of Hox genes. The Hox transcription factors, as we will see in Chapters 13 and 19 specify the type of vertebrae at each particular axial level (ribbed thoracic vertebrae, unribbed abdominal vertebrae, etc.). Without functioning Rpl38, vertebral cells are unable to form the initiation complex with mRNA from the appropriate Hox genes, and the skeleton is deformed (FIGURES A, B). Mutations in other ribosomal proteins have also been found to produce deficient phenotypes (Terzian and Box 2013; Watkins-Chow et al. 2013).
Model of ribosomal heterogeneity in mice. (A) Ribosomes have slightly different proteins depending on the tissue in which they reside. Ribosomal protein Rpl38 (i.e., protein 38 of the large ribosomal subunit) is concentrated in those ribosomes found in the somites that give rise to the vertebrae. (B) A wild-type embryo (left) has normal vertebrae and normal Hox gene translation. Mice deficient in Rpl38 have an extra pair of vertebrae, tail deformities, and reduced Hox gene translation. (After N. Kondrashov et al. 2011. Cell 145: 383–397.)