Author: Blank, Maximilian F.; Chen, Sifan; Poetz, Fabian; Schnölzer, Martina; Voit, Renate; Grummt, Ingrid
Title: SIRT7-dependent deacetylation of CDK9 activates RNA polymerase II transcription Document date: 2017_3_17
ID: qm9urt2w_2
Snippet: Previous work has established that SIRT7 is a key regulator of nucleolar transcription and pre-rRNA processing. SIRT7 is enriched in nucleoli and activates RNA polymerase I (Pol I) transcription by deacetylating PAF53 (Polymerase-Associated Factor 53), a core subunit of mammalian Pol I (12) . Hypoacetylation of PAF53 enhances pre-rRNA synthesis by facilitating the association of Pol I with rDNA, thereby promoting Pol I transcription. Additionally.....
Document: Previous work has established that SIRT7 is a key regulator of nucleolar transcription and pre-rRNA processing. SIRT7 is enriched in nucleoli and activates RNA polymerase I (Pol I) transcription by deacetylating PAF53 (Polymerase-Associated Factor 53), a core subunit of mammalian Pol I (12) . Hypoacetylation of PAF53 enhances pre-rRNA synthesis by facilitating the association of Pol I with rDNA, thereby promoting Pol I transcription. Additionally, SIRT7 regulates processing of pre-rRNA by deacetylating U3-55k, a core component of the U3 snoRNP complex. Reversible acetylation modulates the association of U3-55k protein with U3 snoRNA, deacetylation by SIRT7 enhancing the interaction (13) . Upon exposure to cellular stress, SIRT7 is released from nucleoli and accumulates in the nu-cleoplasm, which leads to hyperacetylation of both PAF53 and U3-55k and defects in transcription and processing of pre-rRNA. These results indicated that SIRT7 controls ribosome biogenesis through a mechanism involving binding to pre-rRNA and U3 snoRNA as well as nucleolarnucleoplasmic shuttling in response to stress signaling. The role of SIRT7 in ribosome biogenesis and cell proliferation is also supported by recent proteomic analyses showing that SIRT7 is associated with numerous non-nucleolar target proteins with functions in transcription, ribosome biogenesis and translation (14) (15) (16) . SIRT7 was also found to interact with chromatin remodeling complexes, such as B-WICH, NoRC and SWI/SNF, which are required for the establishment of a specific chromatin structure. Furthermore, SIRT7 was shown to occupy tRNA genes and to interact with Pol III and TFIIIC2, suggesting a regulatory role of SIRT7 in Pol III transcription (14, 16) .
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