Эукариоттарда РНҚ полимераза I және рибосомалық РНҚ синтезі

Enzyme in eukaryotes
RNA polymerase 1 (also known as Pol I) is, in higher eukaryotes, the polymerase that only transcribes ribosomal RNA (but not 5S rRNA, which is synthesized by RNA polymerase III), a type of RNA that accounts for over 50% of the total RNA synthesized in a cell.

Pol I is a 590 kDa enzyme that consists of 14 protein subunits (polypeptides), and its crystal structure in the yeast Saccharomyces cerevisiae was solved at 2.8Å resolution in 2013. Twelve of its subunits have identical or related counterparts in RNA polymerase II (Pol II) and RNA polymerase III (Pol III). The other two subunits are related to Pol II initiation factors and have structural homologues in Pol III. Ribosomal DNA transcription is confined to the nucleolus, where about 400 copies of the 42.9 kb rDNA gene are present, arranged as tandem repeats in nucleolus organizer regions. Each copy contains a ~13.3 kb sequence encoding the 18S, the 5.8S, and the 28S RNA molecules, interlaced with two internal transcribed spacers, ITS1 and ITS2, and flanked upstream by a 5' external transcribed spacer and a downstream 3' external transcribed spacer. These components are transcribed together to form the 45S pre rRNA. The 45S pre rRNA is then post transcriptionally cleaved by C/D box and H/ACA box snoRNAs, removing the two spacers and resulting in the three rRNAs by a complex series of steps. The 5S ribosomal RNA is transcribed by Pol III. Because of the simplicity of Pol I transcription, it is the fastest acting polymerase and contributes up to 60% of cellular transcription levels in exponentially growing cells. In Saccharomyces cerevisiae, the 5S rDNA has the unusual feature of lying inside the rDNA repeat. It is flanked by non transcribed spacers NTS1 and NTS2, and is transcribed backwards by Pol III, separately from the rest of the rDNA. Two specific mechanisms have been identified, ensuring proper control of rRNA synthesis and Pol I mediated transcription. Given the large numbers of rDNA genes (several hundreds) available for transcription, the first mechanism involves adjustments in the number of genes being transcribed at a specific time. In mammalian cells, the number of active rDNA genes varies between cell types and level of differentiation. In general, as a cell becomes more differentiated, it requires less growth and, therefore, will have a decrease in rRNA synthesis and a decrease in rDNA genes being transcribed. When rRNA synthesis is stimulated, SL1 (selectivity factor 1) will bind to the promoters of rDNA genes that were previously silent, and recruit a pre initiation complex to which Pol I will bind and start transcription of rRNA. Changes in rRNA transcription can also occur via changes in the rate of transcription. While the exact mechanism through which Pol I increases its rate of transcription is as yet unknown, evidence has shown that rRNA synthesis can increase or decrease without changes in the number of actively transcribed rDNA.

Pol I requires no TATA box in the promoter, instead relying on an upstream control element (UCE) located between −200 and −107, and a core element located between −45 and +20. The dimeric eukaryotic upstream binding factor (UBF) binds the UCE and the core element. UBF recruits and binds a protein complex called SL1 in humans (or TIF IB in mouse), composed of the TATA binding protein (TBP) and three TBP associated factors (TAFs). The UBF dimer contains several high mobility group boxes (HMG boxes) that introduce loops into the upstream region, allowing the UCE and the core elements to come into contact. RRN3/TIF IA is phosphorylated and binds Pol I.
Pol I binds to the UBF/SL1 complex via RRN3/TIF IA, and transcription starts. Note that this process is variable in different organisms.