rRNA processing

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R-HSA-72312
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Pathway
Species
Homo sapiens
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Each eukaryotic cytosolic ribosome contains 4 molecules of RNA: 28S rRNA (25S rRNA in yeast), 5.8S rRNA, and 5S rRNA in the 60S subunit and 18S rRNA in the 40S subunit. The 18S rRNA, 5.8S rRNA, and 28S rRNA are produced by endonucleolytic and exonucleolytic processing of a single 47S precursor (pre-rRNA) (reviewed in Henras et al. 2015). Transcription of ribosomal RNA genes, processing of pre-rRNA, and assembly of precursor 60S and 40S subunits occur in the nucleolus (reviewed in Hernandez-Verdun et al. 2010), with a few late reactions occurring in the cytosol. Within the nucleolus non-transcribed DNA and inactive polymerase complexes are located in the fibrillar center, active DNA polymerase I transcription occurs at the interface between the fibrillar center and the dense fibrillar component, early processing of pre-rRNA occurs in the dense fibrillar component, and late processing of pre-rRNA occurs in the granular component (Stanek et al. 2001).
Processed ribosomal RNA contains many modified nucleotides which are generated by enzymes acting on encoded nucleotides contained in the precursor rRNA (reviewed in Boschi-Muller and Motorin 2013). The most numerous modifications are pseudouridine residues and 2'-O-methylribonucleotides. Pseudouridylation is guided by base pairing between the precursor rRNA and a small nucleolar RNA (snoRNA) in a Box C/D snoRNP (reviewed in Henras et al 2004, Yu and Meier 2014). Similarly, 2'-O-methylation is guided by base pairing between the precursor rRNA and a snoRNA in a Box H/ACA snoRNP (reviewed in Henras et al. 2004, Hamma and Ferre-D'Amare 2010). Other modifications include N(1)-methylpseudouridine, 5-methylcytosine, 7-methylguanosine, 6-dimethyladenosine, and 4-acetylcytidine. Modification of nucleotides occur as the pre-rRNA is being cleaved. However, the order of cleavage and modification steps is not clear so these two processes are presented separately here. Defects in ribosome biogenesis factors can cause disease (reviewed in Freed et al. 2010).
Mitochondrial ribosomes are completely distinct from cytoplasmic ribosomes, having different protein subunits and 12S rRNA and 16S rRNA. The mitochondrial rRNAs are encoded in the mitochondrial genome and are produced by processing of a long H strand transcript. Specific residues in the rRNAs are modified by enzymes to yield 5 different types of modified nucleotides:

Literature References
PubMed ID Title Journal Year
11862453 Non-isotopic mapping of ribosomal RNA synthesis and processing in the nucleolus

Stanek, D, Koberna, K, Pliss, A, Malínský, J, Masata, M, Vecerová, J, Risueño, MC, Raska, I

Chromosoma 2001
24490730 Chemistry enters nucleic acids biology: enzymatic mechanisms of RNA modification

Boschi-Muller, S, Motorin, Y

Biochemistry Mosc. 2013
20174677 When ribosomes go bad: diseases of ribosome biogenesis

Freed, EF, Bleichert, F, Dutca, LM, Baserga, SJ

Mol Biosyst 2010
19917616 The box H/ACA ribonucleoprotein complex: interplay of RNA and protein structures in post-transcriptional RNA modification

Hamma, T, Ferré-D'Amaré, AR

J. Biol. Chem. 2010
15193314 RNA structure and function in C/D and H/ACA s(no)RNPs

Henras, AK, Dez, C, Henry, Y

Curr. Opin. Struct. Biol. 2004
25346433 An overview of pre-ribosomal RNA processing in eukaryotes

Henras, AK, Plisson-Chastang, C, O'Donohue, MF, Chakraborty, A, Gleizes, PE

Wiley Interdiscip Rev RNA 2015
21956940 The nucleolus: structure/function relationship in RNA metabolism

Hernandez-Verdun, D, Roussel, P, Thiry, M, Sirri, V, Lafontaine, DL

Wiley Interdiscip Rev RNA 2010
25590339 RNA-guided isomerization of uridine to pseudouridine--pseudouridylation

Yu, YT, Meier, UT

RNA Biol 2014
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