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Revision as of 11:54, 6 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,081 edits Saving copy of the {{chembox}} taken from revid 459125230 of page Pseudouridine for the Chem/Drugbox validation project (updated: 'CASNo').		Latest revision as of 15:43, 8 November 2024 edit Ira Leviton (talk | contribs)Extended confirmed users333,876 edits Fixed a reference and deleted an unneeded jargon abbreviation. Please see Category:CS1 errors: dates and Category:CS1 maint: PMC format.
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			{{short description|Chemical compound}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|chembox}}) taken from revid of page ] with values updated to verified values.}}
	{{chembox		{{chembox
			| Verifiedfields = changed
	| verifiedrevid = 444468798
			| verifiedrevid = 464375889
	|ImageFile=Pseudouridine.svg
			| ImageFile=Pseudouridine.svg
	|ImageSize=150px
			| ImageSize=150px
	|PIN = 5-(β-D-ribofuranosyl)pyrimidine-2,4(1''H'',3''H'')-dione
	|IUPACName=5--1''H''-pyrimidine-2,4-dione		| IUPACName=5-(β-<small>D</small>-Ribofuranosyl)pyrimidine-2,4(1''H'',3''H'')-dione
			| SystematicName=5-pyrimidine-2,4(1''H'',3''H'')-dione
	|OtherNames=psi-Uridine, 5-Ribosyluracil, beta-D-Pseudouridine, 5-(beta-D-Ribofuranosyl)uracil
			| OtherNames=psi-Uridine, 5-Ribosyluracil, beta-D-Pseudouridine, 5-(beta-D-Ribofuranosyl)uracil
	|Section1={{Chembox Identifiers		|Section1={{Chembox Identifiers
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| CASNo_Ref = {{cascite|correct|CAS}}
			| CASNo=1445-07-4
			| Beilstein = 32779
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 14319		| ChemSpiderID = 14319
			| ChEMBL = 3144027
			| KEGG = C02067
			| UNII_Ref = {{fdacite|correct|FDA}}
			| UNII = 7R0R6H6KEG
			| PubChem=15047
			| ChEBI_Ref = {{ebicite|correct|EBI}}
			| ChEBI = 17802
	| InChI = 1/C9H12N2O6/c12-2-4-5(13)6(14)7(17-4)3-1-10-9(16)11-8(3)15/h1,4-7,12-14H,2H2,(H2,10,11,15,16)/t4-,5-,6-,7+/m1/s1		| InChI = 1/C9H12N2O6/c12-2-4-5(13)6(14)7(17-4)3-1-10-9(16)11-8(3)15/h1,4-7,12-14H,2H2,(H2,10,11,15,16)/t4-,5-,6-,7+/m1/s1
	| InChIKey = PTJWIQPHWPFNBW-GBNDHIKLBY		| InChIKey = PTJWIQPHWPFNBW-GBNDHIKLBY
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	| InChI1 = 1S/C9H12N2O6/c12-2-4-5(13)6(14)7(17-4)3-1-10-9(16)11-8(3)15/h1,4-7,12-14H,2H2,(H2,10,11,15,16)/t4-,5-,6-,7+/m1/s1		| InChI1 = 1S/C9H12N2O6/c12-2-4-5(13)6(14)7(17-4)3-1-10-9(16)11-8(3)15/h1,4-7,12-14H,2H2,(H2,10,11,15,16)/t4-,5-,6-,7+/m1/s1
	| InChIKey1 = PTJWIQPHWPFNBW-GBNDHIKLSA-N		| InChIKey1 = PTJWIQPHWPFNBW-GBNDHIKLSA-N
	| CASNo_Ref = {{cascite|correct|??}}
	| CASNo = <!-- blanked - oldvalue: 1445-07-4 -->
	| PubChem=15047
	| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 17802
	| SMILES = O=C1N\C=C(/C(=O)N1)2O(CO)(O)2O		| SMILES = O=C1N\C=C(/C(=O)N1)2O(CO)(O)2O
	}}		}}
	|Section2={{Chembox Properties		|Section2={{Chembox Properties
	| Formula=C<sub>9</sub>H<sub>12</sub>N<sub>2</sub>O<sub>6</sub>		| Formula=C<sub>9</sub>H<sub>12</sub>N<sub>2</sub>O<sub>6</sub>
	| MolarMass=244.20 g/mol		| MolarMass=244.20 g/mol
	| Appearance=White granular powder		| Appearance=White granular powder
	| Density=		| Density=
	| MeltingPt=		| MeltingPt=
	| BoilingPt=		| BoilingPt=
	| Solubility= Highly soluble in water.		| Solubility= Highly soluble in water.
	}}		}}
	|Section3={{Chembox Hazards		|Section3={{Chembox Hazards
	| MainHazards=		| MainHazards=
	| FlashPt=		| FlashPt=
			| AutoignitionPt =
	| Autoignition=
	}}		}}
	}}		}}
			'''Pseudouridine''' ('''5-ribosyluracil''', abbreviated by the Greek letter psi- '''Ψ''')<ref name=":0">{{Cite journal|last1=Hamma|first1=Tomoko|last2=Ferré-D'Amaré|first2=Adrian R.|date=November 2006|title=Pseudouridine Synthases|journal=Chemistry & Biology|volume=13|issue=11|pages=1125–1135|doi=10.1016/j.chembiol.2006.09.009|pmid=17113994|issn=1074-5521|doi-access=free}}</ref> is an ] of the ] ] in which the ] is attached via a carbon-carbon instead of a nitrogen-carbon ].
			Pseudouridine is the most abundant ] in cellular ]<ref>{{Cite journal |last1=Penzo |first1=Marianna |last2=Guerrieri |first2=Ania |last3=Zacchini |first3=Federico |last4=Treré |first4=Davide |last5=Montanaro |first5=Lorenzo |date=2017-11-01 |title=RNA Pseudouridylation in Physiology and Medicine: For Better and for Worse |journal=Genes |language=en |volume=8 |issue=11 |pages=301 |doi=10.3390/genes8110301 |issn=2073-4425 |pmc=5704214 |pmid=29104216|doi-access=free }}</ref> and one of over 100 chemically distinct modifications that may affect translation or other functions of RNA. Pseudouridine is the C5-] isomer of uridine that contains a ] between C1 of the ] and C5 of ], rather than usual C1-N1 bond found in uridine. Uridine is converted to pseudouridine by rotating the uridine molecule 180° across its N3-C6 axis.<ref name="pmid34556550">{{cite journal | vauthors = Garus A, Autexier C | title = Dyskerin: an essential pseudouridine synthase with multifaceted roles in ribosome biogenesis, splicing, and telomere maintenance | journal = ] | volume = 27 | issue=12 | pages = 1441–1458 | date=2021 | doi = 10.1261/rna.078953.121 | pmc=8594475 | pmid = 34556550}}</ref> The C-C bond gives it more rotational freedom and conformational flexibility.<ref name=":3">{{Cite journal|last=Gray|first=Michael Charette, Michael W.|date=2000-05-01|title=Pseudouridine in RNA: What, Where, How, and Why|journal=IUBMB Life |volume=49|issue=5|pages=341–351|doi=10.1080/152165400410182|pmid=10902565|s2cid=20561376 |issn=1521-6543|doi-access=}}</ref> In addition, pseudouridine has an extra hydrogen bond donor at the N1 position.
			Pseudouridine is a ubiquitous constituent of structural RNA (], ], ] (snRNA) and ]), and present in mRNA, across the three phylogenetic domains of life and was the first discovered. It accounts for 4% of the nucleotides in ] ].<ref>{{Cite journal |last=Davis |first=F. F. |last2=Allen |first2=F. W. |date=October 1957 |title=Ribonucleic acids from yeast which contain a fifth nucleotide |url=https://pubmed.ncbi.nlm.nih.gov/13463012/ |journal=The Journal of Biological Chemistry |volume=227 |issue=2 |pages=907–915 |issn=0021-9258 |pmid=13463012}}</ref> This base modification is able to stabilize RNA and improve base-stacking by forming additional hydrogen bonds with water through its extra imino group.<ref>{{Cite journal |last=Davis |first=Darrell R. |date=1995 |title=Stabilization of RNA stacking by pseudouridine |journal=Nucleic Acids Research |language=en |volume=23 |issue=24 |pages=5020–5026 |doi=10.1093/nar/23.24.5020 |issn=0305-1048 |pmc=307508 |pmid=8559660}}</ref> There are 11 pseudouridines in '']'' rRNA, 30 in yeast cytoplasmic rRNA and a single modification in mitochondrial 21S rRNA and about 100 pseudouridines in human rRNA indicating that the extent of pseudouridylation increases with the complexity of an organism.<ref>{{cite journal |last1=Ofengand |first1=J |last2=Bakin |first2=A |title=Mapping to nucleotide resolution of pseudouridine residues in large subunit ribosomal RNAs from representative eukaryotes, prokaryotes, archaebacteria, mitochondria and chloroplasts |journal=Journal of Molecular Biology |date=1997-02-21 |volume=266 |issue=2 |pages=246–268 |doi=10.1006/jmbi.1996.0737 |pmid=9047361 |doi-access=free }}</ref> Pseudouridine was also detected in the '']'' genome. 18 pseudouridine modification sites were detected in the ] entry site and in the mRNA entry tunnel in protein translation. These modifications in the parasite lead to increased protein synthesis and growth rate.<ref>{{cite journal |last1=Bussotti |first1=Giovanni |last2=Piel |first2=Laura |last3=Pescher |first3=Pascale |last4=Domagalska |first4=Malgorzata A. |last5=Rajan |first5=K. Shanmugha |last6=Cohen-Chalamish |first6=Smadar |last7=Doniger |first7=Tirza |last8=Hiregange |first8=Disha-Gajanan |last9=Myler |first9=Peter J. |last10=Unger |first10=Ron |last11=Michaeli |first11=Shulamit |last12=Späth |first12=Gerald F. |title=Genome instability drives epistatic adaptation in the human pathogen Leishmania |journal=Proceedings of the National Academy of Sciences |date=21 December 2021 |volume=118 |issue=51 |pages=e2113744118 |doi=10.1073/pnas.2113744118 |pmid=34903666 |pmc=8713814 |bibcode=2021PNAS..11813744B |language=en |issn=0027-8424|doi-access=free }}</ref>
			Pseudouridine in ] and tRNA has been shown to fine-tune and stabilize the regional structure and help maintain their functions in mRNA decoding, ribosome assembly, processing and translation.<ref name=":3" /><ref>{{Cite journal|last1=Ge|first1=Junhui|last2=Yu|first2=Yi-Tao|date=April 2013|title=RNA pseudouridylation: new insights into an old modification|journal=Trends in Biochemical Sciences|volume=38|issue=4|pages=210–218|doi=10.1016/j.tibs.2013.01.002|pmid=23391857|pmc=3608706|issn=0968-0004}}</ref><ref name=":2">{{Cite journal|last1=Rintala-Dempsey|first1=Anne C.|last2=Kothe|first2=Ute|date=2017-01-03|title=Eukaryotic stand-alone pseudouridine synthases – RNA modifying enzymes and emerging regulators of gene expression?|journal=RNA Biology|volume=14|issue=9|pages=1185–1196|doi=10.1080/15476286.2016.1276150|pmid=28045575|pmc=5699540|issn=1547-6286}}</ref> Pseudouridine in ] has been shown to enhance ] RNA-pre-mRNA interaction to facilitate splicing regulation.<ref>{{Cite journal|last1=Wu|first1=Guowei|last2=Radwan|first2=Mohamed K.|last3=Xiao|first3=Mu|last4=Adachi|first4=Hironori|last5=Fan|first5=Jason|last6=Yu|first6=Yi-Tao|date=2016-06-07|title=TheTORsignaling pathway regulates starvation-induced pseudouridylation of yeast U2 snRNA|journal=RNA|volume=22|issue=8|pages=1146–1152|doi=10.1261/rna.056796.116|pmid=27268497|pmc=4931107|issn=1355-8382}}</ref>
			]
			== Effects and modification on different RNA ==
			=== tRNA ===
			]Ψ is ubiquitous in this class of RNAs and facilitates common ] ]s. One such structural motif is the TΨC stem loop which incorporates Ψ55. Ψ is commonly found in the D stem and anticodon stem and loop of tRNAs from each domain. In each structural motif the unique physicochemical properties of Ψ stabilize structures that would not be possible with the standard U.<ref name=":3"/>
			During translation Ψ modulates interactions of tRNA molecules with ] and ]. Ψ and other modified nucleotides affect the local structure of the tRNA domains they are found in without impacting the overall fold of the RNA. In the ] ] (ASL) Ψ seems critical for proper binding of tRNAs to the ribosome. Ψ stabilizes the dynamic structure of the ASL and promotes stronger binding to the 30S ribosome. The stabilized conformation of the ASL helps maintain correct ]-] pairings during translation. This stability may increase translational accuracy by decreasing the rate of peptide bond formation and allowing for more time for incorrect codon-anticodon pairs to be rejected. Despite Ψ’s role in local structure stabilization, pseudouridylation of tRNA is not essential for cell viability and is not usually required for ].<ref name=":3" />
			=== mRNA ===
			Ψ is also found in ] which are the template for protein synthesis. Ψ residues in mRNA can affect the coding specificity of stop codons UAA, UGA, and UAG. In these stop codons both a U→Ψ modification and a U→C mutation both promote nonsense suppression.<ref>{{Cite journal|last1=Adachi|first1=Hironori|last2=De Zoysa|first2=Meemanage D.|last3=Yu|first3=Yi-Tao|date=March 2019|title=Post-transcriptional pseudouridylation in mRNA as well as in some major types of noncoding RNAs|journal=Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms|volume=1862|issue=3|pages=230–239|doi=10.1016/j.bbagrm.2018.11.002|pmid=30414851|pmc=6401265|issn=1874-9399}}</ref> In the SARS-CoV2 vaccine from BioNTech/Pfizer, also known as ], tozinameran or Comirnaty, all U's have been substituted with ],<ref>{{Cite web|date=2021-02-19|title=European medicines Agency Assessment report on Comirnaty (Common name: COVID-19 mRNA vaccine) (nucleoside-modified) Procedure No. EMEA/H/C/005735/0000|url=https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf}}</ref> a nucleoside related to Ψ that contains a methyl group added to N1 atom.
			=== rRNA ===
			Ψ is found in the large and small ] subunits of all domains of life and their ]s. In the ribosome Ψ residues cluster in domains II, IV, and V and stabilize RNA-RNA and/or RNA-protein interactions. The stability afforded by Ψ may assist ] folding and ribosome assembly. Ψ may also influence the stability of local structures which impact the speed and accuracy of decoding and proofreading during translation.<ref name=":3" />
			=== snRNA ===
			Ψ is found in the major ] ] of eukaryotes. Ψ residues in snRNA are often phylogenetically conserved, but have some variations across taxa and organisms. The Ψ residues in snRNAs are normally located in regions that participate in RNA-RNA and/or RNA-protein interactions involved in the assembly and function of the spliceosome. Ψ residues in snRNAS contribute to the proper folding and assembly of the spliceosome which is essential for pre-mRNA processing.<ref name=":3" />
			== Synthases ==
			Pseudouridine are RNA modifications that are done ], so after the RNA is formed {{Citation needed|reason=The article states " are RNA modifications that are done post-transcriptionally". Martinez et al., 2022 suggest through their experiments that it occurs co-transcriptionally (https://doi.org/10.1016/j.molcel.2021.12.023).|date=December 2022}}. The proteins that do this modification are called pseudouridine synthases (PUS) and are found in all kingdoms of life. Most research has been done on how PUS modify tRNA, so mechanisms involving snRNA, and mRNA are not clearly defined. PUS can vary on RNA specificity, structure, and ] mechanisms. The different structures of PUS are divided into five families which share the active sequence and important structural motifs.<ref name=":0"/>
			=== TruA ===
			TruA domain modifies a variety of different places in tRNA, snRNA, and mRNA. The mechanism of isomerization of uridine is still being talked about in this family.<ref name=":2" /><ref name=":5">{{Cite journal|date=2017-11-01|title=RNA Pseudouridylation in Physiology and Medicine: For Better and for Worse|journal=Genes|volume=8|issue=11|pages=301|doi=10.3390/genes8110301|pmid=29104216|pmc=5704214|issn=2073-4425|last1=Penzo|first1=M.|last2=Guerrieri|first2=A. N.|last3=Zacchini|first3=F.|last4=Treré|first4=D.|last5=Montanaro|first5=L.|doi-access=free}}</ref>
			]
			'''PUS 1''' is located in the nucleus and modifies tRNA at different locations, U44 of U2 snRNA, and U28 of U6 snRNA. Studies found that PUS 1 expression increased during environmental stress and is important for regulating the splicing of RNA. Also, that PUS 1 is necessary for taking the tRNA made in the nucleus and sending them to the cytoplasm.<ref name=":2" />
			'''PUS 2''' is very similar to PUS 1, but located in the mitochondria and only modifies U27 and U28 of mito-tRNA. This protein modifies the mitochondrial tRNA, which has a lesser amount of pseudouridine modifications compared to other tRNAs. Unlike most mitochondria located protein, PUS 2 has not been found to have a mitochondrial targeting signal or MTS.<ref name=":2" />
			'''PUS 3''' is a homolog to PUS 1, but modifies different places of the tRNA (U38/39) in the cytoplasm and mitochondrial. This protein is the most conserved of the TruA family. A decrease in modifications made by PUS 3 was found when the tRNA structure of improperly folded. Along with tRNA the protein targets ncRNA and mRNA, further research is still needed as to the importance of this modification. PUS 3 along with PUS 1 modify the steroid activator receptor in humans.<ref name=":2" />
			=== TruB ===
			The TruB family only contains PUS 4 located in the mitochondrial and nucleus. PUS 4 modification is heavily conserved located in the U55 in the elbow of the tRNA. The human form of PUS 4 is actually missing a binding domain called PUA or pseudouridine synthase and ] trans-glycosylase. PUS 4 has a sequence specificity for T-loop part of the tRNA. Preliminary data of PUS4 modifying mRNA, but more research is needed to confirm. Also binds to a specific Brome Mosaic Virus, which is a plant-infecting RNA virus.<ref name=":2" /><ref>{{Cite journal|last1=Keffer-Wilkes|first1=Laura Carole|last2=Veerareddygari|first2=Govardhan Reddy|last3=Kothe|first3=Ute|date=2016-11-14|title=RNA modification enzyme TruB is a tRNA chaperone|journal=Proceedings of the National Academy of Sciences|volume=113|issue=50|pages=14306–14311|doi=10.1073/pnas.1607512113|pmid=27849601|pmc=5167154|bibcode=2016PNAS..11314306K |issn=0027-8424|doi-access=free}}</ref>
			=== TruD ===
			TruD is able to modify a variety of RNA, and it is unclear how these different RNA substrates are recognized. PUS 7 modifies U2 snRNA at the position 35 and this modification will increase when the cells are in heat shock. Another modification is cytoplasmic tRNA in position 13, and position 35 in pre-tRNA<sup>Tyr</sup>. PUS 7 modifies almost specificity does not depend on the type of RNA as mRNA show pseudouridylated by PUS 7. Recognize this the sequence of the RNA, UGUAR with the second U being the nucleotide that will be modified. The pseudouridylation of mRNA by PUS 7 increases during heat shock, because the protein moves from the nucleus to the cytoplasm. The modification is thought to increase the stability of mRNA during heat shock before the RNA goes to the nucleus or mitochondria, but more studies are needed.<ref name=":2" /><ref name=":5" />
			=== RluA ===
			The RluA domain of these proteins can identify the substrate through a different protein binding to the substrate and then particular bonds to the RluA domain.<ref name=":0" /><ref name=":5" />
			'''PUS 5''' is not well studied and located pseudouridine synthase and similar to Pus 2 does not have a mitochondrial signal targeting sequence. The protein modifies U2819 of mitochondrial 21S rRNA. Also suspected that Pus 5 modifies some uridines in the mRNA, but again more data is needed to confirm.
			'''PUS 6''' has one that only modifies U31 of cytoplasmic and mitochondrial tRNA. Pus 6 is also known to modify mRNA.<ref name=":2" />
			'''PUS 8''' also known as Rib2 modifies cytoplasmic tRNA at position U32. On the C-terminus there is a DRAP-deaminase domain related to the biosynthesis of riboflavin. The RluA and DRAP or deaminase domain related to ] have completely separate functions in the protein and it is not known whether they interact with each other. PUS 8 is necessary in yeast, but that is suspected to be related to the riboflavin synthesis and not the pseudouridine modification.<ref name=":2" />
			'''PUS 9''' and PUS 8 catalyze the same position in mitochondrial tRNA instead of cytoplasmic. It is the only PUS protein that contains a mitochondrial targeting signal domain on the N-terminus. Studies suggest that PUS 9 can modify mRNAs, which would mean less substrate specificity.<ref name=":2" />
			=== RsuA ===
			{{empty section|date=July 2022}}
			== Techniques in genome sequencing for pseudouridine ==
			Pseudouridine can be identified through a multitude of different techniques. A common technique to identify modifications in RNA and DNA is Liquid Chromatography with Mass Spectrometry or ]. ] separates molecules by the mass and charge. While uridine and pseudouridine have the same mass, they have different charges. ] works by retention time, which has to do with leaving the column.<ref>{{Cite journal|date=2017-09-05|title=Quantification of Pseudouridine Levels in Cellular RNA Pools with a Modified HPLC-UV Assay|journal=Genes|volume=8|issue=9|pages=219|doi=10.3390/genes8090219|pmid=28872587|pmc=5615352|issn=2073-4425|last1=Xu|first1=J.|last2=Gu|first2=A. Y.|last3=Thumati|first3=N. R.|author4=Wong JMY|doi-access=free}}</ref> A chemical way to identify pseudouridine uses a compound called CMC or N-cyclohexyl-N′-β-(4-methylmorpholinium) ethylcarbodiimide to specifically label and distinguish uridine from pseudouridine.<ref>{{cite journal |last1=Bakin |first1=A |title=Four newly located pseudouridylate residues in Escherichia coli 23S ribosomal RNA are all at the peptidyltransferase center: analysis by the application of a new sequencing technique |journal=Biochemistry |date=1993-09-21 |volume=32 |issue=37 |pages=9754–9762 |doi=10.1021/bi00088a030 |pmid=8373778 |url=https://pubs.acs.org/doi/abs/10.1021/bi00088a030}}</ref> CMC will bond both with pseudouridine and uridine, but holds tighter to the former, because of the third nitrogen able to form hydrogen bond. CMC bound to pseudouridine can then be imaged by tagging a signaling molecule. This method is still being worked on to become high-throughput.<ref>{{Cite journal|title=Faculty of 1000 evaluation for Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA.|last=Kalsotra|first=Auinash|date=2016-11-02|doi = 10.3410/f.718875945.793524920|doi-access=free}}</ref>
			An improved technique, 2-bromoacrylamide-assisted cyclization sequencing, enables Ψ-to-C transitions, for quantitative profiling of Ψ at single-base resolution.<ref>{{Cite journal |last=Xu |first=Haiqi |last2=Kong |first2=Linzhen |last3=Cheng |first3=Jingfei |last4=Al Moussawi |first4=Khatoun |last5=Chen |first5=Xiufei |last6=Iqbal |first6=Aleema |last7=Wing |first7=Peter A. C. |last8=Harris |first8=James M. |last9=Tsukuda |first9=Senko |last10=Embarc-Buh |first10=Azman |last11=Wei |first11=Guifeng |last12=Castello |first12=Alfredo |last13=Kriaucionis |first13=Skirmantas |last14=McKeating |first14=Jane A. |last15=Lu |first15=Xin |date=November 2024 |title=Absolute quantitative and base-resolution sequencing reveals comprehensive landscape of pseudouridine across the human transcriptome |url=https://www.nature.com/articles/s41592-024-02439-8 |journal=Nature Methods |language=en |volume=21 |issue=11 |pages=2024–2033 |doi=10.1038/s41592-024-02439-8 |issn=1548-7105 |pmc=11541003 |pmid=39349603}}</ref>
			== Medical relevance of pseudouridine ==
			Pseudouridine exerts a subtle but significant influence on the nearby sugar-phosphate backbone and also enhances base stacking. These effects may underlie the biological role of most, but perhaps not all of the pseudouridine residues in RNA. Certain genetic mutants lacking specific pseudouridine residues in tRNA or rRNA exhibit difficulties in translation, display slow growth rates, and fail to compete effectively with wild-type strains in mixed culture. Pseudouridine modifications are also implicated in human diseases such as ] and ] (MLASA) and Dyskeratosis congenita.<ref name=":2"/> ] and ] are two rare inherited syndromes caused by mutations in ], the gene encoding for the pseudouridine synthase dyskerin. Pseudouridines have been recognized as regulators of viral latency processes in human immunodeficiency virus (]) infections.<ref name=":4">{{Cite journal|last1=Zhao|first1=Yang|last2=Karijolich|first2=John|last3=Glaunsinger|first3=Britt|last4=Zhou|first4=Qiang|date=October 2016|title=Pseudouridylation of 7 SK sn RNA promotes 7 SK sn RNP formation to suppress HIV -1 transcription and escape from latency|journal=EMBO Reports|volume=17|issue=10|pages=1441–1451|doi=10.15252/embr.201642682|pmid=27558685|pmc=5048380|issn=1469-221X}}</ref> Pseudouridylation has also been associated with the pathogenesis of maternally inherited diabetes and deafness (MIDD). In particular, a point mutation in a mitochondrial tRNA seems to prevent the pseudouridylation of one nucleotide, thus altering the tRNA tertiary structure. This may lead to higher tRNA instability, causing deficiencies in mitochondrial translation and respiration.<ref name=":4" />
			=== Vaccines ===
			When pseudouridine is used in place of uridine in synthetic mRNA, the modified mRNA molecule arouses less response from ], a part of the human immune system that would otherwise identify the mRNA as unwelcome. This makes pseudouridine useful in ], including the mRNA ]s. This property of pseudouridine was discovered by ] and ] in 2005, for which they shared the ].<ref>{{cite news |url=https://www.nature.com/articles/d41586-021-02483-w |title=The tangled history of mRNA vaccines |work=] |date=September 14, 2021 |last=Dolgin |first=Elie}}</ref><ref>{{Cite web |title=The Nobel Prize in Physiology or Medicine 2023 |url=https://www.nobelprize.org/prizes/medicine/2023/press-release/ |access-date=2023-10-02 |website=NobelPrize.org |language=en-US}}</ref>
			] provides even less innate immune response than Ψ, as well as improving ] capacity.<ref name="pmid34611326">{{cite journal | vauthors = Morais P, Adachi H, Yu Y | title = The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines | journal = ] | volume = 9 | pages = 789427 | date = 2021 | doi = 10.3389/fcell.2021.789427 | pmc = 8600071 | pmid = 34805188| doi-access = free }}</ref> Both ] and ] mRNA vaccines therefore use N1-Methylpseudouridine rather than Ψ.<ref name="pmid34611326" />
			==See also==
			*]
			*]
			*]
			==References==
			{{reflist}}
			]
			]