SIRT7

Sirtuin 7
Identifiers
Symbols SIRT7 ; SIR2L7
External IDs OMIM: 606212 MGI: 2385849 HomoloGene: 56152 GeneCards: SIRT7 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 51547 209011
Ensembl ENSG00000187531 ENSMUSG00000025138
UniProt Q9NRC8 Q8BKJ9
RefSeq (mRNA) NM_016538 NM_153056
RefSeq (protein) NP_057622 NP_694696
Location (UCSC) Chr 17:
81.91 – 81.92 Mb		 Chr 11:
120.62 – 120.63 Mb
PubMed search

NAD-dependent deacetylase sirtuin-7 is an enzyme that in humans is encoded by the SIRT7 gene.[1][2][3]

Function

This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class IV of the sirtuin family.[3]

In humans cells, SIRT7 has only been shown to interact with two other molecules: RNA polymerase I (RNA Pol I) and upstream binding factor (UBF).[2] SIRT7 is localized to the nucleolus and interacts with RNA Pol I. Chromatin immunoprecipitation studies demonstrate that SIRT7 localizes to rDNA, and coimmunoprecipitation shows that SIRT7 binds RNA Pol I. In addition SIRT7 interacts with UBF, a major component of the RNA Pol I initiation complex.[4] It is not known whether or not SIRT7 is modifying RNA Pol I and/or UBF, and if so, what those modifications are.

SIRT7 is expressed more in metabolically active tissues, such as liver and spleen, and less in non-proliferating tissues, such as heart and brain.[2] Furthermore, it has been shown that SIRT7 is necessary for rDNA transcription. Knock down of SIRT7 in HEK293 cells resulted in decreased rRNA levels. This same study found that this SIRT3 knockdown decreased the amount of RNA Pol I associated with rDNA, suggesting that SIRT7 may be required for rDNA transcription. Knock down SIRT7 led to reduced RNA Pol I levels, but RNA Pol I mRNA levels did not change. This suggests that SIRT7 plays a crucial role in connecting the function of chromatin remodeling complexes to RNA Pol I machinery during transcription.[5]

SIRT7 may help attenuate DNA damage and thereby promoting cellular survival under conditions of genomic stress.[6]

Clinical relevance

This gene has been found to be involved in maintenance of oncogenic transformation.[7]

References

  1. ↑ Frye RA (Jul 2000). "Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins". Biochemical and Biophysical Research Communications 273 (2): 793–8. doi:10.1006/bbrc.2000.3000. PMID 10873683.
  2. 1 2 3 Ford E, Voit R, Liszt G, Magin C, Grummt I, Guarente L (May 2006). "Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription". Genes & Development 20 (9): 1075–80. doi:10.1101/gad.1399706. PMC 1472467. PMID 16618798.
  3. 1 2 "Entrez Gene: SIRT7 sirtuin (silent mating type information regulation 2 homolog) 7 (S. cerevisiae)".
  4. ↑ Grob A, Roussel P, Wright JE, McStay B, Hernandez-Verdun D, Sirri V (Feb 2009). "Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis". Journal of Cell Science 122 (Pt 4): 489–98. doi:10.1242/jcs.042382. PMC 2714433. PMID 19174463.
  5. ↑ Tsai YC, Greco TM, Boonmee A, Miteva Y, Cristea IM (Feb 2012). "Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription". Molecular & Cellular Proteomics 11 (2): M111.015156. doi:10.1074/mcp.M111.015156. PMC 3277772. PMID 22147730.
  6. ↑ Mohrin M, Shin J, Liu Y, Brown K, Luo H, Xi Y, Haynes CM, Chen D (Mar 2015). "Stem cell aging. A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging". Science 347 (6228): 1374–7. doi:10.1126/science.aaa2361. PMID 25792330.
  7. ↑ Barber MF, Michishita-Kioi E, Xi Y, Tasselli L, Kioi M, Moqtaderi Z, Tennen RI, Paredes S, Young NL, Chen K, Struhl K, Garcia BA, Gozani O, Li W, Chua KF (Jul 2012). "SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation". Nature 487 (7405): 114–8. doi:10.1038/nature11043. PMC 3412143. PMID 22722849.

Further reading


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