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

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. © 2010 juge et al.