NSUN2

NOP2/Sun domain family, member 2 is a protein that in humans is encoded by the NSUN2 gene.[5] Alternatively spliced transcript variants encoding different isoforms have been noted for the gene.

NSUN2
Identifiers
AliasesNSUN2, MISU, MRT5, SAKI, TRM4, NOP2/Sun RNA methyltransferase family member 2, NOP2/Sun RNA methyltransferase 2
External IDsOMIM: 610916 MGI: 107252 HomoloGene: 9817 GeneCards: NSUN2
Orthologs
SpeciesHumanMouse
Entrez

54888

28114

Ensembl

ENSG00000037474

ENSMUSG00000021595

UniProt

Q08J23

Q1HFZ0

RefSeq (mRNA)

NM_001193455
NM_017755

NM_145354

RefSeq (protein)

NP_001180384
NP_060225

NP_663329

Location (UCSC)Chr 5: 6.6 – 6.63 MbChr 13: 69.68 – 69.78 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

The protein is a methyltransferase that catalyzes the methylation of cytosine to 5-methylcytosine (m5C) at position 34 of intron-containing tRNA (Leu)(CAA) precursors. This modification is necessary to stabilize the anticodon-codon pairing and correctly translate the mRNA.[5] NSUN2 is also localized on mitochondria and is capable of introducing post-transcriptional modifications in mitochondrial tRNAs.[6][7]

Clinical relevance

Mutations in this gene have been found associated to cases of Dubowitz-like syndrome.[8]

Model organisms

Model organisms have been used in the study of NSUN2 function. A conditional knockout mouse line, called Nsun2tm1a(EUCOMM)Wtsi[23][24] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[25][26][27]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[21][28] Twenty eight tests were carried out on mutant mice and fourteen significant abnormalities were observed. Homozygous mutants were subviable and had decreased body weights, length of long bones and decreased circulating glucose levels, numerous abnormal body composition, X-ray imaging, eye morphology and haematology parameters; males also had a decreased grip strength, a short upturned snout, and abnormal indirect calorimetry and plasma chemistry parameters.[21] Males (but not females) were also infertile.[21] In addition, heterozygote mutants displayed premature hair follicle exogen.[21]

References
  1. GRCh38: Ensembl release 89: ENSG00000037474 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000021595 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "NOP2/Sun domain family, member 2". Retrieved 2011-12-04.
  6. Shinoda S, Kitagawa S, Nakagawa S, Wei FY, Tomizawa K, Araki K, et al. (July 2019). "Mammalian NSUN2 introduces 5-methylcytidines into mitochondrial tRNAs". Nucleic Acids Research. 47 (16): 8734–8745. doi:10.1093/nar/gkz575. PMC 6895283. PMID 31287866.
  7. Van Haute L, Lee SY, McCann BJ, Powell CA, Bansal D, Vasiliauskaitė L, et al. (July 2019). "NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs". Nucleic Acids Research. 47 (16): 8720–8733. doi:10.1093/nar/gkz559. PMC 6822013. PMID 31276587.
  8. Martinez FJ, Lee JH, Lee JE, Blanco S, Nickerson E, Gabriel S, et al. (June 2012). "Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome". Journal of Medical Genetics. 49 (6): 380–5. doi:10.1136/jmedgenet-2011-100686. PMC 4771841. PMID 22577224.
  9. "Body weight data for Nsun2". Wellcome Trust Sanger Institute.
  10. "Grip strength data for Nsun2". Wellcome Trust Sanger Institute.
  11. "Dysmorphology data for Nsun2". Wellcome Trust Sanger Institute.
  12. "Indirect calorimetry data for Nsun2". Wellcome Trust Sanger Institute.
  13. "Glucose tolerance test data for Nsun2". Wellcome Trust Sanger Institute.
  14. "DEXA data for Nsun2". Wellcome Trust Sanger Institute.
  15. "Radiography data for Nsun2". Wellcome Trust Sanger Institute.
  16. "Eye morphology data for Nsun2". Wellcome Trust Sanger Institute.
  17. "Clinical chemistry data for Nsun2". Wellcome Trust Sanger Institute.
  18. "Haematology data for Nsun2". Wellcome Trust Sanger Institute.
  19. "Salmonella infection data for Nsun2". Wellcome Trust Sanger Institute.
  20. "Citrobacter infection data for Nsun2". Wellcome Trust Sanger Institute.
  21. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
  22. Mouse Resources Portal, Wellcome Trust Sanger Institute.
  23. "International Knockout Mouse Consortium".
  24. "Mouse Genome Informatics".
  25. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, et al. (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  26. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  27. Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  28. van der Weyden L, White JK, Adams DJ, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading
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