Abstract
SummarySen1 of S. cerevisiae is a known component of the NRD complex implicated in transcription termination of nonpolyadenylated as well as some polyadenylated RNA polymerase II transcripts. We now show that Sen1 helicase possesses a wider function by restricting the occurrence of RNA:DNA hybrids that may naturally form during transcription, when nascent RNA hybridizes to DNA prior to its packaging into RNA protein complexes. These hybrids displace the nontranscribed strand and create R loop structures. Loss of Sen1 results in transient R loop accumulation and so elicits transcription-associated recombination. SEN1 genetically interacts with DNA repair genes, suggesting that R loop resolution requires proteins involved in homologous recombination. Based on these findings, we propose that R loop formation is a frequent event during transcription and a key function of Sen1 is to prevent their accumulation and associated genome instability.
Highlights
In S. cerevisiae nascent transcripts formed by RNA polymerase II (Pol II) on protein-coding genes are immediately processed, packaged, and exported to the cytoplasm (Luna et al, 2008; Moore and Proudfoot, 2009)
Sen1 of S. cerevisiae is a known component of the NRD complex implicated in transcription termination of nonpolyadenylated as well as some polyadenylated RNA polymerase II transcripts
We show that Sen1 helicase possesses a wider function by restricting the occurrence of RNA:DNA hybrids that may naturally form during transcription, when nascent RNA hybridizes to DNA prior to its packaging into RNA protein complexes
Summary
In S. cerevisiae nascent transcripts formed by RNA polymerase II (Pol II) on protein-coding genes are immediately processed, packaged, and exported to the cytoplasm (Luna et al, 2008; Moore and Proudfoot, 2009). Deletion of genes encoding the THO (Thp, Hpr, Mft, and Tho2) and THSC or TREX-2 (Thp, Sac, Sus, and Cdc31) complexes required for mRNP formation in S. cerevisiae—or, the splicing factor ASF/SF2 in metazoans—increase levels of R loop formation and TAM and TAR (Chavez et al, 2000; Fischer et al, 2002; Gallardo and Aguilera, 2001; Gonzalez-Aguilera et al, 2008; Huertas and Aguilera, 2003; Li and Manley, 2005). R loop formation in these mutants may be connected to Pol II stalling, interfering with processive elongation (Mason and Struhl, 2005; Rondon et al, 2003) and RNA processing (Libri et al, 2002; Rougemaille et al, 2008). DNA replication may be compromised when replication forks encounter R loops or a stalled Pol II (Wellinger et al, 2006)
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