rRNA processing (Homo sapiens)

From WikiPathways

Jump to: navigation, search
2, 4, 5, 11, 12, 17...3, 6-10, 13...cytosolmitochondrionmitochondrial matrixnucleoplasmpre-MT-TFpre-MT-TL1pre-MT-TVMT-ND4L mRNAMT-ND4 mRNApre-MT-TRpre-MT-TTrRNA processing inthe nucleus andcytosolHSD17B10 16S rRNApre-MT-TDMT-ND1 mRNATRMT10C pre-MT-TS2MT-ATP6 mRNApre-MT-TL2pre-MT-THMT-CO2 mRNApre-MT-TWMT-ATP8 mRNA12S rRNApre-MT-TMpre-MT-TGH strand transcriptMT-CO3 mRNAmtRNase Ppre-MT-TKMT-CYB mRNAMT-ND5 mRNAMT-ND3 mRNAMT-CO1 mRNApre-MT-TIrRNA modification inthe mitochondrionMT-ND2 mRNAKIAA0391 ELAC2221611, 17, 201, 313, 19


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: View original pathway at Reactome.


Pathway is converted from Reactome ID: 72312
Reactome version: 74
Reactome Author 
Reactome Author: Joshi-Tope, G

Quality Tags

Ontology Terms



View all...
  1. Rorbach J, Minczuk M.; ''The post-transcriptional life of mammalian mitochondrial RNA.''; PubMed Europe PMC Scholia
  2. Freed EF, Bleichert F, Dutca LM, Baserga SJ.; ''When ribosomes go bad: diseases of ribosome biogenesis.''; PubMed Europe PMC Scholia
  3. Van Haute L, Pearce SF, Powell CA, D'Souza AR, Nicholls TJ, Minczuk M.; ''Mitochondrial transcript maturation and its disorders.''; PubMed Europe PMC Scholia
  4. Yu YT, Meier UT.; ''RNA-guided isomerization of uridine to pseudouridine--pseudouridylation.''; PubMed Europe PMC Scholia
  5. Henras AK, Dez C, Henry Y.; ''RNA structure and function in C/D and H/ACA s(no)RNPs.''; PubMed Europe PMC Scholia
  6. Vilardo E, Rossmanith W.; ''Molecular insights into HSD10 disease: impact of SDR5C1 mutations on the human mitochondrial RNase P complex.''; PubMed Europe PMC Scholia
  7. Haack TB, Kopajtich R, Freisinger P, Wieland T, Rorbach J, Nicholls TJ, Baruffini E, Walther A, Danhauser K, Zimmermann FA, Husain RA, Schum J, Mundy H, Ferrero I, Strom TM, Meitinger T, Taylor RW, Minczuk M, Mayr JA, Prokisch H.; ''ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy.''; PubMed Europe PMC Scholia
  8. Sanchez MI, Mercer TR, Davies SM, Shearwood AM, Nygård KK, Richman TR, Mattick JS, Rackham O, Filipovska A.; ''RNA processing in human mitochondria.''; PubMed Europe PMC Scholia
  9. Levinger L, Serjanov D.; ''Pathogenesis-related mutations in the T-loops of human mitochondrial tRNAs affect 3' end processing and tRNA structure.''; PubMed Europe PMC Scholia
  10. Li F, Liu X, Zhou W, Yang X, Shen Y.; ''Auto-inhibitory Mechanism of the Human Mitochondrial RNase P Protein Complex.''; PubMed Europe PMC Scholia
  11. Henras AK, Plisson-Chastang C, O'Donohue MF, Chakraborty A, Gleizes PE.; ''An overview of pre-ribosomal RNA processing in eukaryotes.''; PubMed Europe PMC Scholia
  12. Hamma T, Ferré-D'Amaré AR.; ''The box H/ACA ribonucleoprotein complex: interplay of RNA and protein structures in post-transcriptional RNA modification.''; PubMed Europe PMC Scholia
  13. Brzezniak LK, Bijata M, Szczesny RJ, Stepien PP.; ''Involvement of human ELAC2 gene product in 3' end processing of mitochondrial tRNAs.''; PubMed Europe PMC Scholia
  14. Reinhard L, Sridhara S, Hällberg BM.; ''Structure of the nuclease subunit of human mitochondrial RNase P.''; PubMed Europe PMC Scholia
  15. Howard MJ, Lim WH, Fierke CA, Koutmos M.; ''Mitochondrial ribonuclease P structure provides insight into the evolution of catalytic strategies for precursor-tRNA 5' processing.''; PubMed Europe PMC Scholia
  16. Ofman R, Ruiter JP, Feenstra M, Duran M, Poll-The BT, Zschocke J, Ensenauer R, Lehnert W, Sass JO, Sperl W, Wanders RJ.; ''2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency is caused by mutations in the HADH2 gene.''; PubMed Europe PMC Scholia
  17. Boschi-Muller S, Motorin Y.; ''Chemistry enters nucleic acids biology: enzymatic mechanisms of RNA modification.''; PubMed Europe PMC Scholia
  18. Vilardo E, Nachbagauer C, Buzet A, Taschner A, Holzmann J, Rossmanith W.; ''A subcomplex of human mitochondrial RNase P is a bifunctional methyltransferase--extensive moonlighting in mitochondrial tRNA biogenesis.''; PubMed Europe PMC Scholia
  19. Rossmanith W.; ''Localization of human RNase Z isoforms: dual nuclear/mitochondrial targeting of the ELAC2 gene product by alternative translation initiation.''; PubMed Europe PMC Scholia
  20. Hernandez-Verdun D, Roussel P, Thiry M, Sirri V, Lafontaine DL.; ''The nucleolus: structure/function relationship in RNA metabolism.''; PubMed Europe PMC Scholia
  21. Stanek D, Koberna K, Pliss A, Malínský J, Masata M, Vecerová J, Risueño MC, Raska I.; ''Non-isotopic mapping of ribosomal RNA synthesis and processing in the nucleolus.''; PubMed Europe PMC Scholia
  22. Holzmann J, Frank P, Löffler E, Bennett KL, Gerner C, Rossmanith W.; ''RNase P without RNA: identification and functional reconstitution of the human mitochondrial tRNA processing enzyme.''; PubMed Europe PMC Scholia


View all...
113516view11:59, 2 November 2020ReactomeTeamReactome version 74
112714view16:11, 9 October 2020ReactomeTeamReactome version 73
101630view11:49, 1 November 2018ReactomeTeamreactome version 66
101166view21:36, 31 October 2018ReactomeTeamreactome version 65
100692view20:08, 31 October 2018ReactomeTeamreactome version 64
100242view16:54, 31 October 2018ReactomeTeamreactome version 63
99794view15:19, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93586view11:28, 9 August 2017ReactomeTeamreactome version 61
86693view09:24, 11 July 2016ReactomeTeamNew pathway

External references


View all...
NameTypeDatabase referenceComment
12S rRNARnaENST00000389680 (Ensembl)
16S rRNARnaENST00000387347 (Ensembl)
ELAC2ProteinQ9BQ52 (Uniprot-TrEMBL)
H strand transcriptR-HSA-6786802 (Reactome)
HSD17B10 ProteinQ99714 (Uniprot-TrEMBL)
KIAA0391 ProteinO15091 (Uniprot-TrEMBL)
MT-ATP6 mRNARnaENST00000361899 (Ensembl)
MT-ATP8 mRNARnaENST00000361851 (Ensembl)
MT-CO1 mRNARnaENST00000361624 (Ensembl)
MT-CO2 mRNARnaENST00000361739 (Ensembl)
MT-CO3 mRNARnaENST00000362079 (Ensembl)
MT-CYB mRNARnaENST00000361789 (Ensembl)
MT-ND1 mRNARnaENST00000361390 (Ensembl)
MT-ND2 mRNARnaENST00000361453 (Ensembl)
MT-ND3 mRNARnaENST00000361227 (Ensembl)
MT-ND4 mRNARnaENST00000361381 (Ensembl)
MT-ND4L mRNARnaENST00000361335 (Ensembl)
MT-ND5 mRNARnaENST00000361567 (Ensembl)
TRMT10C ProteinQ7L0Y3 (Uniprot-TrEMBL)
mtRNase PComplexR-HSA-6785726 (Reactome)
pre-MT-TDRnaENST00000387419 (Ensembl)
pre-MT-TFRnaENST00000387314 (Ensembl)
pre-MT-TGRnaENST00000387429 (Ensembl)
pre-MT-THRnaENST00000387441 (Ensembl)
pre-MT-TIRnaENST00000387365 (Ensembl)
pre-MT-TKRnaENST00000387421 (Ensembl)
pre-MT-TL1RnaENST00000386347 (Ensembl)
pre-MT-TL2RnaENST00000387456 (Ensembl)
pre-MT-TMRnaENST00000387377 (Ensembl)
pre-MT-TRRnaENST00000387439 (Ensembl)
pre-MT-TS2RnaENST00000387449 (Ensembl)
pre-MT-TTRnaENST00000387460 (Ensembl)
pre-MT-TVRnaENST00000387342 (Ensembl)
pre-MT-TWRnaENST00000387382 (Ensembl)
rRNA modification in the mitochondrionPathwayR-HSA-6793080 (Reactome) Five modified nucleotides have been detected in the 12S rRNA: 5-methylcytidine-841 catalyzed by NSUN4, 6-dimethyladenosine-936 catalyzed by TFB1M, 6-dimethyladenosine-937 catalyzed by TFB1M, 5-methyluridine-429, and 4-methylcytidine-839 (reviewed in Van Haute et al. 2015). Four modified nucleotides have been detected in 16S rRNA: 2'-O-methylguanosine-1145 catalyzed by MRM1, 2'-O-methylguanosine-1370 catalyzed by RNMTL1 (MRM3), 2'-O-methyluridine-1369 catalyzed by FTSJ2 (MRM2), and pseudouridine-1397. 2'-O-methyluridine-1369 and 2'-O-methylguanosone-1370 occur in the A-loop of rRNA which is located at the peptidyl transferase center of the large subunit. Here the modified residues play a role in interaction with the aminoacyl site of tRNA. Knockouts of TFB1M and NSUN4 are lethal in mice and mutations in TFB1M may be related to aminoglycoside-induced deafness (reviewed in Van Haute et al. 2015).
rRNA processing in

the nucleus and

PathwayR-HSA-8868773 (Reactome) 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, modification of nucleotide residues within the rRNA, and assembly of precursor 60S and 40S subunits occur predominantly in the nucleolus (reviewed in Hernandez-Verdun et al. 2010, Boschi-Muller and Motorin 2013), with a few late reactions occurring in the cytosol.

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
12S rRNAArrowR-HSA-6785722 (Reactome)
16S rRNAArrowR-HSA-6785722 (Reactome)
ELAC2mim-catalysisR-HSA-6785722 (Reactome)
H strand transcriptR-HSA-6785722 (Reactome)
MT-ATP6 mRNAArrowR-HSA-6785722 (Reactome)
MT-ATP8 mRNAArrowR-HSA-6785722 (Reactome)
MT-CO1 mRNAArrowR-HSA-6785722 (Reactome)
MT-CO2 mRNAArrowR-HSA-6785722 (Reactome)
MT-CO3 mRNAArrowR-HSA-6785722 (Reactome)
MT-CYB mRNAArrowR-HSA-6785722 (Reactome)
MT-ND1 mRNAArrowR-HSA-6785722 (Reactome)
MT-ND2 mRNAArrowR-HSA-6785722 (Reactome)
MT-ND3 mRNAArrowR-HSA-6785722 (Reactome)
MT-ND4 mRNAArrowR-HSA-6785722 (Reactome)
MT-ND4L mRNAArrowR-HSA-6785722 (Reactome)
MT-ND5 mRNAArrowR-HSA-6785722 (Reactome)
R-HSA-6785722 (Reactome) RNase P, ELAC2, and additional unknown nucleases cleave H strand transcripts to release the various tRNAs, rRNAs, and mRNAs contained in the long polycistronic transcripts.
Mitochondrial RNase P, comprising 3 protein subunits and no RNA moiety (Holzmann et al. 2008), endonucleolytically cleaves polycistronic mitochondrial transcripts at the 5' ends of the tRNA sequences (Sanchez et al. 2011, Howard et al. 2012, Vilardo et al. 2012, Li et al. 2015, Reinhard et al. 2015, Vilardo and Rossmanith 2015). A subcomplex of RNase P also functions as a tRNA methyltransferase and the SDR5C1 subunit is an amino acid and fatty acid dehydrogenase. Mutations in the SDR5C1 subunit of RNase P cause HSD10 disease, which is characterized by progressive neurodegeneration and cardiomyopathy (Vilardo and Rossmanith 2015)
ELAC2 cleaves polycistronic mitochondrial transcripts at the 3' ends of the tRNA sequences (Brzezniak et al. 2011, Sanchez et al. 2011). Different isoforms of ELAC2 are present in the nucleus and mitochondria (Rossmanith 2011). Mutations in ELAC2 cause cardiac hypertrophy (Haack et al. 2013) and disorders of oxidative phosphorylation (reviewed in Van Haute et al. 2015).
Unknown nucleases also cleave the H strand transcript at sites 5' to MT-CO3, 5' to MT-CO1, and 5' to MT-CYB (reviewed in Van Haute et al. 2015).
mtRNase PArrowR-HSA-6785722 (Reactome)
pre-MT-TDArrowR-HSA-6785722 (Reactome)
pre-MT-TFArrowR-HSA-6785722 (Reactome)
pre-MT-TGArrowR-HSA-6785722 (Reactome)
pre-MT-THArrowR-HSA-6785722 (Reactome)
pre-MT-TIArrowR-HSA-6785722 (Reactome)
pre-MT-TKArrowR-HSA-6785722 (Reactome)
pre-MT-TL1ArrowR-HSA-6785722 (Reactome)
pre-MT-TL2ArrowR-HSA-6785722 (Reactome)
pre-MT-TMArrowR-HSA-6785722 (Reactome)
pre-MT-TRArrowR-HSA-6785722 (Reactome)
pre-MT-TS2ArrowR-HSA-6785722 (Reactome)
pre-MT-TTArrowR-HSA-6785722 (Reactome)
pre-MT-TVArrowR-HSA-6785722 (Reactome)
pre-MT-TWArrowR-HSA-6785722 (Reactome)
Personal tools