Synthesis of eukaryotic 28S, 18S and 5.8S rRNA:

In  theeukaryotes,  the  genes  for 18S  , 28S and  5.8S  rRNA  are  classically  clustered both and tandemly repeated in which one copy each of 5.8S, 18S and then 28S genes  occur,  followed  through untranscribed  spacer  DNA,  then  another  group of 18S,

28S and 5.8S genes occur and so on which are shown in the picture. In humans,  there  are about  200 copies  of  this  rRNA  transcription  unit  arranged  as  five  clusters  of  about  40 copies  on  divided  chromosomes.   Those rRNA transcription units are transcribed by RNA polymerase I (RNA Pol I) in a region of the nucleus known as the nucleolus. The nucleolus contains loops of DNA extending from every of the rRNA gene clusters on the various chromosomes and therefore each cluster is known as a nucleolar organizer.

The rRNA promoter consists of a core element that straddles the transcriptional  begin  site (designated  as position 1) from  residues 31 to 6 plus  an upstream  control  components  (UCE)  about  50-80  bp  in  size  and  located  about 100 bp upstream from the begin site for example at position -100. A transcription factor known as upstream binding factor (UBF) binds both to the UCE as well as to a region next to and overlapping with the core component.  Interestingly, TATA box binding protein (TBP), also binds to the rRNA promoter (in reality, TBP is needs for initiation through all three eukaryotic RNA polymerases). The TBP and UBF transcription factors interact with each other and with RNA Pol I to form a transcription initiation complex. The RNA Pol I then transcribes the overall transcription unit of 18S, 28S and 5.8S genes to synthesize a single large pre-rRNA molecule.

In the humans,  the product  of transcription  is a 45S pre-rRNA  that  has non- rRNA ETSs external transcribed  spacers at the 5'  and 3'  ends and non-rRNA internal  transcribed  spacers  (ITSs)  inside  dividing  the rRNA  sequences shown in the figure. This 45S molecule folds up to form a described secondary structure with stem-loops,ribosomal proteins bind to chosen sequences methylation of ribose moieties occurs at over 100 nucleotides and more than 100 uridine residues are modified to pseudouridine (ψ). The 45S pre-rRNA molecule is then cleaved first in the ETSs and then in the ITSs to release precursor  rRNAs which are cleaved further and trimmed to release the mature 18S, 28S, and 5.8S rRNAs which is described in above diagram.

In the eukaryotes, selection of the sites  in  pre-rRNA  which  will  be  methylated depends upon small RNAs found in the nucleolus known as small nucleolar RNAs (snoRNAs)  which  exist  in  ribonucleoprotein  complexes   known as  snoRNPs. The snoRNAs  hold  long  regions  (10-21  nt) which  are complementary to specific regions of the pre-rRNA  molecule form base pairs with the pre-rRNA  at these sites  and  then  guide where  methylation of specific  ribosome  residues 2' O methylation and isomerization  of uridine to pseudouridine  will occur.