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Genome-wide function of THO/TREX in active genes prevents R-loop-dependent replication obstacles

AuthorsGómez-González, Belén ; García-Rubio, María L. ; Bermejo, Rodrigo ; Gaillard, Hélène ; Shirahige, Katsuhiko; Marín, Antonio; Foiani, Marco; Aguilera, Andrés
KeywordsReplicant impairment
Issue Date8-Jun-2012
PublisherNature Publishing Group
CitationEMBO Journal 30(15): 3106-3119 (2011)
AbstractTHO/TREX is a conserved nuclear complex that functions in mRNP biogenesis and prevents transcription-associated recombination. Whether or not it has a ubiquitous role in the genome is unknown. Chromatin immunoprecipitation (ChIP)-chip studies reveal that the Hpr1 component of THO and the Sub2 RNA-dependent ATPase have genome-wide distributions at active ORFs in yeast. In contrast to RNA polymerase II, evenly distributed from promoter to termination regions, THO and Sub2 are absent at promoters and distributed in a gradual 5-2 3-2 gradient. This is accompanied by a genome-wide impact of THO->Sub2 deletions on expression of highly expressed, long and high G+C-content genes. Importantly, ChIP-chips reveal an over-recruitment of Rrm3 in active genes in THO mutants that is reduced by RNaseH1 overexpression. Our work establishes a genome-wide function for THO->Sub2 in transcription elongation and mRNP biogenesis that function to prevent the accumulation of transcription-mediated replication obstacles, including R-loops. © 2011 European Molecular Biology Organization.
Identifiersissn: 0261-4189
e-issn: 1460-2075
Appears in Collections:(CABIMER) Artículos
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