Dicer promotes transcription termination at sites of replication stress to maintain genome stability.

Stephane E Castel, Jie Ren, Sonali Bhattacharjee, An-Yun Chang, Mar Sánchez, Alberto Valbuena, Francisco Antequera, Robert A Martienssen

Cell 2014 Oct 23

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Nuclear RNAi is an important regulator of transcription and epigenetic modification, but the underlying mechanisms remain elusive. Using a genome-wide approach in the fission yeast S. pombe, we have found that Dcr1, but not other components of the canonical RNAi pathway, promotes the release of Pol II from the 3? end of highly transcribed genes, and, surprisingly, from antisense transcription of rRNA and tRNA genes, which are normally transcribed by Pol I and Pol III. These Dcr1-terminated loci correspond to sites of replication stress and DNA damage, likely resulting from transcription-replication collisions. At the rDNA loci, release of Pol II facilitates DNA replication and prevents homologous recombination, which would otherwise lead to loss of rDNA repeats especially during meiosis. Our results reveal a novel role for Dcr1-mediated transcription termination in genome maintenance and may account for widespread regulation of genome stability by nuclear RNAi in higher eukaryotes.

Citation

Stephane E Castel, Jie Ren, Sonali Bhattacharjee, An-Yun Chang, Mar Sánchez, Alberto Valbuena, Francisco Antequera, Robert A Martienssen. Dicer promotes transcription termination at sites of replication stress to maintain genome stability. Cell. 2014 Oct 23;159(3):572-83