SIRT7

NAD-dependent deacetylase sirtuin-7 is an is_associated_with::enzyme that in humans is encoded by the SIRT7 is_associated_with::gene.

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.

In humans cells, SIRT7 has only been shown to interact with two other molecules: is_associated_with::RNA polymerase I (RNA Pol I) and is_associated_with::upstream binding factor (UBF). SIRT7 is localized to the nucleolus and interacts with RNA Pol I. is_associated_with::Chromatin immunoprecipitation studies demonstrate that SIRT7 localizes to rDNA, and is_associated_with::coimmunoprecipitation shows that SIRT7 binds RNA Pol I. In addition SIRT7 interacts with UBF, a major component of the RNA Pol I initiation complex. 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. Furthermore, it has been shown that SIRT7 is necessary for rDNA transcription. Knock down of SIRT7 in is_associated_with::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 is_associated_with::chromatin remodeling complexes to RNA Pol I machinery during transcription.

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

Clinical relevance
This gene has been found to be involved in maintenance of oncogenic transformation.