Ribosome biogenesis

Cellular process
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 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. +rRNA found in prokaryotic and eukaryotic ribosomesTypeSizeLarge subunit (LSU rRNA)Small subunit (SSU rRNA)prokaryotic70S50S (5S : 120 nt, 23S : 2906 nt)30S (16S : 1542 nt)eukaryotic80S60S (5S : 121 nt, 5.8S : 156 nt, 28S : 5070 nt)40S (18S : 1869 nt)

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 transcription and translation in prokaryotes.

Ribosomal protein synthesis in eukaryotes is a major metabolic activity. It occurs, like most protein synthesis, in the cytoplasm just outside the nucleus. Individual ribosomal proteins are synthesized and imported into the nucleus through nuclear pores. See nuclear import for more about the movement of the ribosomal proteins into the nucleus. The DNA is transcribed, at a high speed, in the nucleolus, which contains all 45S rRNA genes. The only exception is the 5S rRNA which is transcribed outside the nucleolus. After transcription, the rRNAs associate with the ribosomal proteins, forming the two types of ribosomal subunits (large and small). These will later assemble in the cytosol to make a functioning ribosome. See nuclear export for more about the movement of the ribosomal subunits out of the nucleus.

Eukaryotic cells co transcribe three of the mature rRNA species through a series of steps. The maturation process of the rRNAs and the process of recruiting the r proteins happen in precursor ribosomal particles, sometimes called pre ribosomes, and takes place in the nucleolus, nucleoplasm, and cytoplasm. The yeast, S. cerevisiae is the eukaryotic model organism for the study of ribosome biogenesis. Ribosome biogenesis starts in the nucleolus. There, the 35S pre RNA is transcribed from ribosomal genes as a polycistronic transcript by RNA polymerase I and processed into the 18S, 5.8S, and 25S subunits of the rRNA. At this point in the ribosome biogenesis process, the 40S pre ribosome already shows the “head” and “body” structures of the mature 40S subunit. The 40S pre ribosome is transported out of the nucleolus and into the cytoplasm. The cytoplasmic 40S pre ribosome now contains ribosomal proteins, the 20s rRNA and a few non ribosomal factors. The final formation of the 40S subunit “beak” structure occurs after a phosphorylation and dephosphorylation event involving the Enp1 Ltv1 Rps3 complex and the kinase, Hrr25. Cleavage of the 20S pre rRNA at the D site creates the mature 18s rRNA. This cleavage event is dependent on several non ribosomal factors such as Nob1, Rio1, Rio2, Tsr1 and Fap7.