NSUN2

NOP2/Sun RNA methyltransferase family, member 2
Identifiers
Symbols NSUN2 ; MISU; MRT5; SAKI; TRM4
External IDs OMIM: 610916 HomoloGene: 9817 GeneCards: NSUN2 Gene
EC number 2.1.1.203
Orthologs
Species Human Mouse
Entrez 54888 28114
Ensembl ENSG00000037474 ENSMUSG00000021595
UniProt Q08J23 Q1HFZ0
RefSeq (mRNA) NM_001193455 NM_145354
RefSeq (protein) NP_001180384 NP_663329
Location (UCSC) Chr 5:
6.6 – 6.63 Mb		 Chr 13:
69.53 – 69.64 Mb
PubMed search

NOP2/Sun domain family, member 2 is a protein that in humans is encoded by the NSUN2 gene.[1] Alternatively spliced transcript variants encoding different isoforms have been noted for the gene.

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.[1]

Clinical relevance

Mutations in this gene have been found associated to cases of Dubowitz-like syndrome.[2]

Model organisms

Model organisms have been used in the study of NSUN2 function. A conditional knockout mouse line, called Nsun2tm1a(EUCOMM)Wtsi[17][18] 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.[19][20][21]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[15][22] 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.[15] Males (but not females) were also infertile.[15] In addition, heterozygote mutants displayed premature hair follicle exogen.[15]

References

  1. 1 2 "NOP2/Sun domain family, member 2". Retrieved 2011-12-04.
  2. ↑ Martinez FJ, Lee JH, Lee JE, Blanco S, Nickerson E, Gabriel S, Frye M, Al-Gazali L, Gleeson JG (June 2012). "Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome". J. Med. Genet. 49 (6): 380–5. doi:10.1136/jmedgenet-2011-100686. PMID 22577224.
  3. ↑ "Body weight data for Nsun2". Wellcome Trust Sanger Institute.
  4. ↑ "Grip strength data for Nsun2". Wellcome Trust Sanger Institute.
  5. ↑ "Dysmorphology data for Nsun2". Wellcome Trust Sanger Institute.
  6. ↑ "Indirect calorimetry data for Nsun2". Wellcome Trust Sanger Institute.
  7. ↑ "Glucose tolerance test data for Nsun2". Wellcome Trust Sanger Institute.
  8. ↑ "DEXA data for Nsun2". Wellcome Trust Sanger Institute.
  9. ↑ "Radiography data for Nsun2". Wellcome Trust Sanger Institute.
  10. ↑ "Eye morphology data for Nsun2". Wellcome Trust Sanger Institute.
  11. ↑ "Clinical chemistry data for Nsun2". Wellcome Trust Sanger Institute.
  12. ↑ "Haematology data for Nsun2". Wellcome Trust Sanger Institute.
  13. ↑ "Salmonella infection data for Nsun2". Wellcome Trust Sanger Institute.
  14. ↑ "Citrobacter infection data for Nsun2". Wellcome Trust Sanger Institute.
  15. 1 2 3 4 5 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.
  16. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  17. ↑ "International Knockout Mouse Consortium".
  18. ↑ "Mouse Genome Informatics".
  19. ↑ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  20. ↑ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  21. ↑ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  22. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading


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