Ribosome biogenesis is the process of making ribosomes. In prokaryotes, this process takes place in the cytoplasm with the transcription of many ribosome gene operons. In eukaryotes, it takes place both in the cytoplasm and in the nucleolus. It involves the coordinated function of over 200 proteins in the synthesis and processing of the three prokaryotic or four eukaryotic rRNAs, as well as assembly of those rRNAs with the ribosomal proteins. Most of the ribosomal proteins fall into various energy-consuming enzyme families including ATP-dependent RNA helicases, AAA-ATPases, GTPases, and kinases. About 60% of a cell's energy is spent on ribosome production and maintenance. Ribosome biogenesis is a very tightly regulated process, and it is closely linked to other cellular activities like growth and division. Some have speculated that in the origin of life, ribosome biogenesis predates cells, and that genes and cells evolved to enhance the reproductive capacity of ribosomes. Ribosomes Ribosomes are the macromolecular machines that are responsible for mRNA translation into proteins. The eukaryotic ribosome, also called the 80S ribosome, is made up of two subunits – the large 60S subunit (which contains the 25S [in plants] or 28S [in mammals], 5.8S, and 5S rRNA and 46 ribosomal proteins) and a small 40S subunit (which contains the 18S rRNA and 33 ribosomal proteins). The ribosomal proteins are encoded by ribosomal genes. Prokaryotes There are 52 genes that encode the ribosomal proteins, and they can be found in 20 operons within prokaryotic DNA. Regulation of ribosome synthesis hinges on the regulation of the rRNA itself. First, a reduction in aminoacyl-tRNA will cause the prokaryotic cell to respond by lowering transcription and translation. This occurs through a series of steps, beginning with stringent factors binding to ribosomes and catalyzing the reaction:GTP + ATP --> pppGpp + AMP The γ-phosphate is then removed and ppGpp will bind to and inhibit RNA polymerase. This binding causes a reduction in rRNA transcription. A reduced amount of rRNA means that ribosomal proteins (r-proteins) will be translated but will not have an rRNA to bind to. Instead, they will negatively feedback and bind to their own mRNA, repressing r-protein synthesis. Note that r-proteins preferentially bind to their complementary rRNA if it is present, rather than mRNA. The ribosome operons also include the genes for RNA polymerase and elongation factors (used in RNA translation). Regulation of all of these genes at once illustrate the coupling between