The SR Protein B52/SRp55 Is Required for DNA Topoisomerase I Recruitment to Chromatin, mRNA Release and Transcription Shutdown e1001124

• Published in: PLoS genetics Vol. 6; no. 9
• Main Authors: Juge, François, Fernando, Céline, Fic, Weronika, Tazi, Jamal
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 01.09.2010
• Subjects: Binding sites; Chromatin; Chromosomes; Deoxyribonucleic acid; DNA; Genetic testing; Genotype & phenotype; Kinases; Life sciences; Phosphorylation; Proteins; Recruitment; RNA polymerase
• ISSN: 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1001124

DNA- and RNA-processing pathways are integrated and interconnected in the eukaryotic nucleus to allow efficient gene expression and to maintain genomic stability. The recruitment of DNA Topoisomerase I (Topo I), an enzyme controlling DNA supercoiling and acting as a specific kinase for the SR-protein family of splicing factors, to highly transcribed loci represents a mechanism by which transcription and processing can be coordinated and genomic instability avoided. Here we show that Drosophila Topo I associates with and phosphorylates the SR protein B52. Surprisingly, expression of a high-affinity binding site for B52 in transgenic flies restricted localization, not only of B52, but also of Topo I to this single transcription site, whereas B52 RNAi knockdown induced mis-localization of Topo I in the nucleolus. Impaired delivery of Topo I to a heat shock gene caused retention of the mRNA at its site of transcription and delayed gene deactivation after heat shock. Our data show that B52 delivers Topo I to RNA polymerase II-active chromatin loci and provide the first evidence that DNA topology and mRNA release can be coordinated to control gene expression.