Sus1 is recruited to coding regions and functions during transcription elongation in association with SAGA and TREX2
Pau Pascual-Garcia,Chhabi K. Govind,Ethel Queralt,Bernardo Cuenca-Bono,Ana Llopis,Sebastián Chávez,Alan G. Hinnebusch,Susana Rodríguez-Navarro +7 more
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TLDR
It is shown that Sus1 is required during transcription elongation and is associated with the elongating form of RNA Polymerase II (RNAP II) phosphorylated on Ser5 and Ser2 of the C-terminal domain (CTD), and that Sgf73 is necessary for association of Sus1 with both SAGA and TREX2, and that its absence dramatically reduces Sus1 occupancy of UAS and ORF sequences.Abstract:
Gene transcription, RNA biogenesis, and mRNA transport constitute a complicated process essential for all eukaryotic cells. The transcription/export factor Sus1 plays a key role in coupling transcription activation with mRNA export, and it resides in both the SAGA and TREX2 complexes. Moreover, Sus1 is responsible for GAL1 gene gating at the nuclear periphery, which is important for its transcriptional status. Here, we show that Sus1 is required during transcription elongation and is associated with the elongating form of RNA Polymerase II (RNAP II) phosphorylated on Ser5 and Ser2 of the C-terminal domain (CTD). In addition, Sus1 copurifies with the essential mRNA export factors Yra1 and Mex67, which bind to the mRNA cotranscriptionally. Consistently, ChIP analysis reveals that Sus1 is present at coding regions dependent on transcription in a manner stimulated by Kin28-dependent CTD phosphorylation. Strikingly, eliminating the TREX2 component Sac3 or the SAGA subunit Ubp8 partially impairs Sus1 targeting to coding sequences and upstream activating sequences (UAS). We found, unexpectedly, that Sgf73 is necessary for association of Sus1 with both SAGA and TREX2, and that its absence dramatically reduces Sus1 occupancy of UAS and ORF sequences. Our results reveal that Sus1 plays a key role in coordinating gene transcription and mRNA export by working at the interface between the SAGA and TREX2 complexes during transcription elongation.read more
Citations
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The RNA Polymerase II Carboxy-Terminal Domain (CTD) Code
Dirk Eick,Matthias Geyer +1 more
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Multiple faces of the SAGA complex
TL;DR: The SAGA complex provides a paradigm for multisubunit histone modifying complexes and has important roles in transcript elongation, the regulation of protein stability, and telomere maintenance.
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The Iws1:Spt6:CTD complex controls cotranscriptional mRNA biosynthesis and HYPB/Setd2-mediated histone H3K36 methylation
TL;DR: Iws1 connects two distinct CTD-binding proteins, Spt6 and HYPB/Setd2, in a megacomplex that affects mRNA export as well as the histone modification state of active genes.
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Phosphorylated Pol II CTD recruits multiple HDACs, including Rpd3C(S), for methylation-dependent deacetylation of ORF nucleosomes
Chhabi K. Govind,Chhabi K. Govind,Hongfang Qiu,Daniel S. Ginsburg,Chun Ruan,Kimberly A. Hofmeyer,Cuihua Hu,V. Swaminathan,Jerry L. Workman,Bing Li,Alan G. Hinnebusch +10 more
TL;DR: It is demonstrated that Rpd3, Hos2, and Hda1 have overlapping functions in deacetylating histones and suppressing cotranscriptional histone eviction and a strong correlation between increased acetylation and lower histone occupancy in HDA mutants implies that histone acetylations is important for nucleosome eviction.
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Structural insights into the assembly and function of the SAGA deubiquitinating module.
Nadine L. Samara,Ajit B. Datta,Christopher E. Berndsen,Xiangbin Zhang,Tingting Yao,Robert E. Cohen,Cynthia Wolberger +6 more
TL;DR: The structure of the SAGA deubiquitinating module (DUBm), a four-protein subcomplex, is reported, revealing an arrangement of protein domains that gives rise to a highly interconnected complex, which is stabilized by eight structural zinc atoms that are critical for enzymatic activity.
References
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Journal ArticleDOI
TREX is a conserved complex coupling transcription with messenger RNA export
Katja Sträßer,Seiji Masuda,Paul B. Mason,Jens Pfannstiel,Marisa Oppizzi,Susana Rodríguez-Navarro,Ana G. Rondón,Andrés Aguilera,Kevin Struhl,Robin Reed,Ed Hurt +10 more
TL;DR: The data indicate that the TREX complex has a conserved role in coupling transcription to mRNA export, and is specifically recruited to activated genes during transcription and travels the entire length of the gene with RNA polymerase II.