RNA interference (RNAi) is a widespread gene-silencing mechanism and is required for heterochromatin assembly in a variety of organisms. The RNA-induced transcriptional silencing complex (RITS), composed of Ago1, Tas3 and Chp1, is a key component of RNAi machinery in fission yeast that connects short interference RNA (siRNA) and heterochromatin formation. However, the process by which RITS is assembled is not well understood. Here, we identified Sgf73, a subunit of the SAGA co-transcriptional complex, is required for pericentromeric heterochromatin silencing and the generation of siRNA. This novel role of Sgf73 is independent of enzymatic activities or structural integrity of SAGA. Instead, Sgf73 is physically associated with Ago1 and Chp1. The interactions among the subunits of the RITS, including those between Tas3 and Chp1, between Chp1 and Ago1, between Ago1 and Tas3, were all impaired by the deletion of sgf73(+). Consistently, the recruitment of Ago1 and Chp1 to the pericentromeric region was abolished in sgf73Δ cells. Our study unveils a moonlighting function of a SAGA subunit. It suggests Sgf73 is a novel factor that promotes assembly of RITS and RNAi-mediated heterochromatin formation.
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| http://dx.doi.org/10.1038/srep14707 | DOI Listing |
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UPS writes a new saga of SAGA.
Biochim Biophys Acta Gene Regul Mech
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Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale IL-62901, USA. Electronic address:
SAGA (Spt-Ada-Gcn5-Acetyltransferase), an evolutionarily conserved transcriptional co-activator among eukaryotes, is a large multi-subunit protein complex with two distinct enzymatic activities, namely HAT (Histone acetyltransferase) and DUB (De-ubiquitinase), and is targeted to the promoter by the gene-specific activator proteins for histone covalent modifications and PIC (Pre-initiation complex) formation in enhancing transcription (or gene activation). Targeting of SAGA to the gene promoter is further facilitated by the 19S RP (Regulatory particle) of the 26S proteasome (that is involved in targeted degradation of protein via ubiquitylation) in a proteolysis-independent manner. Moreover, SAGA is also recently found to be regulated by the 26S proteasome in a proteolysis-dependent manner via the ubiquitylation of its Sgf73/ataxin-7 component that is required for SAGA's integrity and DUB activity (and hence transcription), and is linked to various diseases including neurodegenerative disorders and cancer.
View Article and Find Full Text PDFSAGA-CORE subunit Spt7 is required for correct Ubp8 localization, chromatin association and deubiquitinase activity.
Epigenetics Chromatin
October 2020
Gene Expression and RNA Metabolism Laboratory, Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (CSIC), C/Jaume Roig 11, 46010, Valencia, Spain.
Article Synopsis
- Histone H2B deubiquitination, primarily done by Ubp8, is normally linked to the SAGA complex, but this study shows that a DUBm can assemble independently of some SAGA components.
- In experiments, cells lacking the SAGA component SPT7 demonstrated reduced recruitment of Ubp8 and Sus1 to genes and chromatin, indicating the importance of SAGA subunits for Ubp8's location and function.
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Structure of the transcription coactivator SAGA.
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January 2020
Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Göttingen, Germany.
Gene transcription by RNA polymerase II is regulated by activator proteins that recruit the coactivator complexes SAGA (Spt-Ada-Gcn5-acetyltransferase) and transcription factor IID (TFIID). SAGA is required for all regulated transcription and is conserved among eukaryotes. SAGA contains four modules: the activator-binding Tra1 module, the core module, the histone acetyltransferase (HAT) module and the histone deubiquitination (DUB) module.
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Sci Rep
October 2015
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University.
RNA interference (RNAi) is a widespread gene-silencing mechanism and is required for heterochromatin assembly in a variety of organisms. The RNA-induced transcriptional silencing complex (RITS), composed of Ago1, Tas3 and Chp1, is a key component of RNAi machinery in fission yeast that connects short interference RNA (siRNA) and heterochromatin formation. However, the process by which RITS is assembled is not well understood.
View Article and Find Full Text PDFUncovering the role of Sgf73 in maintaining SAGA deubiquitinating module structure and activity.
J Mol Biol
April 2015
Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA. Electronic address:
The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex performs multiple functions in transcription activation including deubiquitinating histone H2B, which is mediated by a subcomplex called the deubiquitinating module (DUBm). The yeast DUBm comprises a catalytic subunit, Ubp8, and three additional subunits, Sgf11, Sus1 and Sgf73, all of which are required for DUBm activity. A portion of the non-globular Sgf73 subunit lies between the Ubp8 catalytic domain and the ZnF-UBP domain and has been proposed to contribute to deubiquitinating activity by maintaining the catalytic domain in an active conformation.
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