rRNA modification in the nucleus and cytosol (Homo sapiens)

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2-6, 12, 16...8, 13, 31, 451, 14, 18, 19, 25...387, 34, 4910, 27, 33, 41132639, 44cytosolnucleoplasmMTADATPDIMT1RCL1 NHP2 Box H/ACA snoRNA FBL pre-rRNANAT10 18SEpre-rRNAcontaining1-methyl-3-aminocarboxypropylpseudoU-1248CoA-SHWBSCR22 Ac-CoAMPHOSPH10 AdoMetNOP228S rRNA containing5-methylC-4447IMP4 RRP9 Box C/D snoRNA ADPDKC1 18SEpre-rRNAcontaining1-methylpseudoU-1248AdoHcy21Spre-rRNAcontaining7-methylG-1639,6-dimethylA-1850,1851Box C/D snoRNPTSR3AdoHcyNOP58 AdoMetNAT10:THUMPD1pre-rRNA containing7-methylG-1639THUMPD1 NHP2L1 AdoMetPiAdoMetIMP3 AdoMetNOP56 AdoHcyTRMT112 Box H/ACA snoRNPSSU ProcessomeNOP10 18SEpre-rRNAcontaining4-acetylcytidine-1377,184218SEpre-rRNAcontaining1-methylpseudoU-1248NOP58 NHP2L1 BMS1 FBL GAR1 WBSCR22:TRIMT112AdoHcyPNO1NOP56 279, 15, 20, 22, 23, 40...131, 18, 32, 43, 5011, 4813261339132724


Description

Human ribosomal RNAs (rRNAs) contain about 200 residues that are enzymatically modified after transcription in the nucleolus (Maden and Khan 1977, Maden 1988, Maden and Hughes 1997, reviewed in Hernandez-Verdun et al. 2010, Boschi-Muller and Motorin 2013). The modified residues occur in regions of the rRNAs that are located in functionally important parts of the ribosome, notably in the A and P peptidyl transfer sites, the polypeptide exit tunnel, and intersubunit contacts (Polikanov et al. 2015, reviewed in Decatur and Fournier 2002, Chow et al. 2007, Sharma and Lafontaine 2015). The two most common modifications are pseudouridines and 2'-O-methylribonucleotides. Formation of pseudouridine from encoded uridine is catalyzed by box H/ACA small nucleolar ribonucleoprotein (snoRNP) complexes (reviewed in Hamma and Ferre-D'Amare 2010, Watkins and Bohnsack 2011, Ge and Yu 2013, Kierzek et al. 2014, Yu and Meier 2014) and methylation of the hydroxyl group of the 2' carbon is catalyzed by box C/D snoRNPs (Kiss-Laszlo et al. 1996, Lapinaite et al. 2013, reviewed in Watkins and Bohnsack 2011). The snoRNP complexes contain common sets of protein subunits and unique snoRNAs that guide each complex to its target nucleotide of the rRNA by base-pairing between the snoRNA and the rRNA (reviewed in Henras et al. 2004, Watkins and Bohnsack 2011). Other modifications of rRNA include 5-methylcytidine (reviewed in Squires and Preiss 2010), 1-methylpseudouridine, 7-methylguanosine, 6-dimethyladenosine, and 4-acetylcytidine (reviewed in Sharma and Lafontaine 2015). In yeast most modifications are introduced co-transcriptionally (Kos and Tollervey 2010, reviewed in Turowski and Tollervey 2015), however the order of modification events and pre-rRNA cleavage events is not well characterized. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 6790901
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: May, Bruce

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Bibliography

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History

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CompareRevisionActionTimeUserComment
114950view16:47, 25 January 2021ReactomeTeamReactome version 75
113394view11:46, 2 November 2020ReactomeTeamReactome version 74
112599view15:57, 9 October 2020ReactomeTeamReactome version 73
101515view11:37, 1 November 2018ReactomeTeamreactome version 66
101051view21:19, 31 October 2018ReactomeTeamreactome version 65
100582view19:53, 31 October 2018ReactomeTeamreactome version 64
100131view16:38, 31 October 2018ReactomeTeamreactome version 63
99681view15:08, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
94497view09:03, 14 September 2017Mkutmonreactome version 61
86675view09:23, 11 July 2016ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
Rna
18SE

pre-rRNA containing

1-methyl-3-aminocarboxypropylpseudoU-1248		R-HSA-8868777 (Reactome)
18SE

pre-rRNA containing

1-methylpseudoU-1248		R-HSA-6790887 (Reactome)
18SE

pre-rRNA containing

1-methylpseudoU-1248		R-HSA-8868782 (Reactome)
18SE

pre-rRNA containing

4-acetylcytidine-1377,1842		R-HSA-6790985 (Reactome)
21S

pre-rRNA containing 7-methylG-1639,

6-dimethylA-1850,1851		R-HSA-6791006 (Reactome) 7-methylguanosine-1639, 6-dimethyladenosine-1850, and 6-dimethyladenosine-1851 refer to the coordinates of the mature 18S rRNA.
28S rRNA containing 5-methylC-4447RnaM11167 (EMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Ac-CoAMetaboliteCHEBI:15351 (ChEBI)
AdoHcyMetaboliteCHEBI:16680 (ChEBI)
AdoMetMetaboliteCHEBI:15414 (ChEBI)
BMS1 ProteinQ14692 (Uniprot-TrEMBL)
Box C/D snoRNA R-HSA-6790639 (Reactome)
Box C/D snoRNPComplexR-HSA-6790894 (Reactome)
Box H/ACA snoRNA R-HSA-6790714 (Reactome)
Box H/ACA snoRNPComplexR-HSA-6790885 (Reactome)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
DIMT1ProteinQ9UNQ2 (Uniprot-TrEMBL)
DKC1 ProteinO60832 (Uniprot-TrEMBL)
FBL ProteinP22087 (Uniprot-TrEMBL)
GAR1 ProteinQ9NY12 (Uniprot-TrEMBL)
IMP3 ProteinQ9NV31 (Uniprot-TrEMBL)
IMP4 ProteinQ96G21 (Uniprot-TrEMBL)
MPHOSPH10 ProteinO00566 (Uniprot-TrEMBL)
MTADMetaboliteCHEBI:17509 (ChEBI)
NAT10 ProteinQ9H0A0 (Uniprot-TrEMBL)
NAT10:THUMPD1ComplexR-HSA-6791007 (Reactome)
NHP2 ProteinQ9NX24 (Uniprot-TrEMBL)
NHP2L1 ProteinP55769 (Uniprot-TrEMBL)
NOP10 ProteinQ9NPE3 (Uniprot-TrEMBL)
NOP2ProteinP46087 (Uniprot-TrEMBL)
NOP56 ProteinO00567 (Uniprot-TrEMBL)
NOP58 ProteinQ9Y2X3 (Uniprot-TrEMBL)
PNO1ProteinQ9NRX1 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:18367 (ChEBI)
RCL1 ProteinQ9Y2P8 (Uniprot-TrEMBL)
RRP9 ProteinO43818 (Uniprot-TrEMBL)
SSU ProcessomeComplexR-HSA-6790891 (Reactome)
THUMPD1 ProteinQ9NXG2 (Uniprot-TrEMBL)
TRMT112 ProteinQ9UI30 (Uniprot-TrEMBL)
TSR3ProteinQ9UJK0 (Uniprot-TrEMBL)
U3 snoRNA Protein
WBSCR22 ProteinO43709 (Uniprot-TrEMBL)
WBSCR22:TRIMT112ComplexR-HSA-6790980 (Reactome)
pre-rRNA containing 7-methylG-1639R-HSA-6790998 (Reactome) 7-methylguanosine-1639 refers to the coordinates of the matue 18S rRNA.
pre-rRNAR-HSA-8856933 (Reactome) A longer precursor transcript that is processed to yield mature rRNAs. This instance of pre-rRNA has no specified length and is used for annotating reactions in which the precursor is not well characterized.

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
18SE

pre-rRNA containing

1-methyl-3-aminocarboxypropylpseudoU-1248		ArrowR-HSA-8868783 (Reactome)
18SE

pre-rRNA containing

1-methylpseudoU-1248		ArrowR-HSA-6790906 (Reactome)
18SE

pre-rRNA containing

1-methylpseudoU-1248		R-HSA-8868783 (Reactome)
18SE

pre-rRNA containing

4-acetylcytidine-1377,1842		ArrowR-HSA-6790987 (Reactome)
21S

pre-rRNA containing 7-methylG-1639,

6-dimethylA-1850,1851		ArrowR-HSA-6790994 (Reactome)
28S rRNA containing 5-methylC-4447ArrowR-HSA-6790944 (Reactome)
ADPArrowR-HSA-6790987 (Reactome)
ATPR-HSA-6790987 (Reactome)
Ac-CoAR-HSA-6790987 (Reactome)
AdoHcyArrowR-HSA-6790906 (Reactome)
AdoHcyArrowR-HSA-6790907 (Reactome)
AdoHcyArrowR-HSA-6790944 (Reactome)
AdoHcyArrowR-HSA-6790982 (Reactome)
AdoHcyArrowR-HSA-6790994 (Reactome)
AdoMetR-HSA-6790906 (Reactome)
AdoMetR-HSA-6790907 (Reactome)
AdoMetR-HSA-6790944 (Reactome)
AdoMetR-HSA-6790982 (Reactome)
AdoMetR-HSA-6790994 (Reactome)
AdoMetR-HSA-8868783 (Reactome)
ArrowR-HSA-6790905 (Reactome)
ArrowR-HSA-6790907 (Reactome)
Box C/D snoRNPmim-catalysisR-HSA-6790907 (Reactome)
Box H/ACA snoRNPmim-catalysisR-HSA-6790905 (Reactome)
CoA-SHArrowR-HSA-6790987 (Reactome)
DIMT1mim-catalysisR-HSA-6790994 (Reactome)
MTADArrowR-HSA-8868783 (Reactome)
NAT10:THUMPD1mim-catalysisR-HSA-6790987 (Reactome)
NOP2mim-catalysisR-HSA-6790944 (Reactome)
PNO1ArrowR-HSA-6790994 (Reactome)
PiArrowR-HSA-6790987 (Reactome)
R-HSA-6790905 (Reactome) Box H/ACA snoRNP complexes convert uridine to pseudouridine at 97 sites in human 28S, 18S, and 5.8S rRNAs (Kiss et al. 2004, reviewed in Ge and Yu 2013). The box H/ACA snoRNA component guides the complex to specific residues of the rRNAs by base pairing between the regions of the snoRNA and the rRNA (Kiss et al. 2004, Xiao et al. 2009). The human genome encodes more than 80 box H/ACA snoRNAs (Lestrade and Weber 2006).
R-HSA-6790906 (Reactome)
R-HSA-6790907 (Reactome)
R-HSA-6790944 (Reactome)
R-HSA-6790982 (Reactome) The WBSCR22:TRMT112 complex, homolog of the Bud23:Trm112 complex in yeast (Ounap et al. 2013), methylates guanosine-1639 of 18S rRNA at the N(7) position of the guanine base (Haag et al. 2015, Zorbas et al. 2015). The WBSCR22:TRMT112 complex but not its methylase activity is required for efficient processing of precursor rRNA at site 2 and site 3 (Haag et al. 2015, Zorbas et al. 2015). Hemizygosity at the region containing WBSCR22 causes Williams-Beuren syndrome (Doll and Grzeschik 2001).
R-HSA-6790987 (Reactome) NAT10 transfers an acetyl group from acetyl coenzyme A to the N4 positions of the residues that will become cytidine 1337 and cytidine-1842 in 18S rRNA (Ito et al. 2014, Sharma et al. 2015). (The point at which NAT10 acts during rRNA nucleolytic processing is unknown.) NAT10 also hydrolyzes ATP, presumably to provide helicase activity for the reaction (Ito et al. 2014, Sharma et al. 2015). NAT10 in a complex with THUMPD1 also acetylates tRNAs, however THUMPD1 is not required for acetylation of rRNA (Sharma et al. 2015).
R-HSA-6790994 (Reactome) DIMT1 (DIMT1L) dimethylates the N(6) position of adenosine-1850 and adenosine-1851 of a precursor to 18S rRNA in the nucleolus (Zorbas et al. 2015). Dimethylation is observed on the 21S precursor and therefore occurs at this stage of rRNA processing or prior. Dimethylation of adenosine residues appears to occur after N(7)-methylation of guanosine-1639 by WBSCR22:TRMT112 (Zorbas et al. 2015). PNO1 is required for the methylation activity of DIMT1 (Zorbas et al. 2015). DIMT1 protein but not DIMT1 methylase activity is also required for efficient concomitant cleavage of 47S precursor rRNA at site A0 and site 1 (Zorbas et al. 2015).
R-HSA-8868783 (Reactome) In the cytoplasm TSR3 transfers an aminocarboxypropyl group from S-adenosylmethionine (AdoMet) to the N(3) position of N(1)-methylpseudouridine at nucleotide 1248 of 18S rRNA yielding N(1)-methyl-N(3)-aminocarboxylpropylpseudouridine-1248 (Meyer et al. 2016). Prior to this reaction, the SNORA13 or ACA13 H/ACA snoRNP (homologue of the snR35 snoRNP in yeast) in the nucleus converts uridine-1248 to pseudouridine-1248 and the EMG1 component of the small subunit processome in the nucleus methylates the N(1) position of pseudouridine-1248. The 18SE precursor of 18S rRNA containing N(1)-methylpseudouridine is then exported to the cytosol as part of the 40S pre-ribosomal subunit. TSR3 is believed to act on the 18SE precursor rather than the mature 18S rRNA because interference with the activity of TSR3 results in an accumulation of 18SE precursor (Meyer et al. 2016).
SSU Processomemim-catalysisR-HSA-6790906 (Reactome)
TSR3mim-catalysisR-HSA-8868783 (Reactome)
WBSCR22:TRIMT112mim-catalysisR-HSA-6790982 (Reactome)
pre-rRNA containing 7-methylG-1639ArrowR-HSA-6790982 (Reactome)
pre-rRNA containing 7-methylG-1639R-HSA-6790994 (Reactome)
pre-rRNAR-HSA-6790982 (Reactome)
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