Does Pol I talk to Pol II? Coordination of RNA polymerases in ribosome biogenesis
- Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland
This extract was created in the absence of an abstract.
To grow and to divide, cells are dependent on protein synthesis, and protein synthesis depends on ribosomes. Ribosomes are complex molecular machines that contain four different RNA molecules and 79 different proteins, produced by three different RNA polymerases. RNA polymerase I (Pol I) synthesizes the large ribosomal RNA (rRNA) precursor (35S RNA in yeast), which is then processed into mature 18S, 28S, and 5.8S RNAs; RNA polymerase II (Pol II) synthesizes the mRNAs encoding the ribosomal proteins; and RNA polymerase III (Pol III) synthesizes the small 5S RNA molecule. The biosynthesis of ribosomes by the three RNA polymerases uses an enormous amount of the cell resources. In a yeast cell, rRNA transcription represents ∼60% of total transcription, and transcription of the ribosomal protein mRNAs represents ∼50% of all Pol II transcription initiation events (Warner 1999; Rudra and Warner 2004). Accordingly, ribosome biosynthesis is tightly regulated with cell growth and proliferation. Thus, when the demand for protein synthesis is reduced, as occurs with cells in stationary phase after nutrient deprivation, the production of new ribosomes is greatly reduced.
Ribosome assembly requires the coordinated production of ribosome components. On the one hand, equimolar amounts of each ribosome protein must be produced. In yeast, the coregulation of ribosomal protein synthesis is exerted mainly at the level of ribosomal protein gene transcription. On the other hand, sufficient amounts of each ribosomal protein must be produced to allow correct assembly and processing of rRNAs. This suggests that the ribosomal protein and rRNA synthesis machineries are somehow coregulated. Indeed, an essential signal transduction pathway for the modulation of rRNA, ribosomal proteins, and 5S rRNA in response to nutrient availability is the TOR (Target of Rapamycin) kinase pathway. This pathway is activated in the presence of nutrients, and inactivation of TOR—for example, by …
