They find that, in metazoan cells, the threat is neutralized by a splicing factor that coats RNA as it it emerges from RNA polymerase... The danger arises because nascent RNA can anneal to the template DNA strand, thus forming an R loop... In eukaryotes, this is not an option as transcription and translation are nuclear and cytoplasmic, respectively... Li and Manley did not set out to discover a genome-protective mechanism, but chanced upon it while studying ASF/SF2... R loop structures appeared during the shut-off, and all these shut-off symptoms could be abolished by overexpression of RNase H, which can degrade the RNA in RNA–DNA hybrids... In vitro, ASF suppressed R loop formation during transcription as long as the transcribing RNA polymerase II was phosphorylated on its COOH-terminal domain, as it is in vivo... This phosphorylated domain was already shown to recruit ASF to the transcription reaction... R loops are not always a bad thing... In B cells they are essential for initiating the DNA rearrangements that mediate class switching of antibody heavy chains... Keeping this machinery away from nascent RNA in other cell types may be one important, presplicing function of ASF and related proteins... Reference: