生命学院学术报告

题目: Dicer functions at sites of replication-transcription collisions to protect genome integrity  

报告人：Jie Ren, Ph.D.（任捷）

Postdoctoral Fellow

Cold Spring Harbor Laboratory

时间：1月11日9:00-10:00

地点：金光生命科学大楼411

Abstract:

Maintaining genome stability and faithfully inheriting the epigenetic information are major challenges in all eukaryotes. Nuclear RNA interference (RNAi) is an important regulator of transcription and epigenetic modifications, however, its function in response to these challenges and the underlying mechanisms remain elusive. Previously, we have shown in Schizosaccharomyces pombe that inheritance of heterochromatin through mitosis requires co-transcriptional RNAi during the DNA replication phase of the cell cycle. Yet the spatial and temporal overlap results in competition between transcription and replication.

We have now found a novel role for the RNAi protein Dicer in resolving replication-transcription collisions via the release of RNA polymerase II (Pol II). This allows Dicer to couple the spreading of heterochromatin with replication fork progression, providing a mechanistic link between heterochromatin inheritance by RNAi and DNA replication. Using genome-wide approaches, we have also revealed that the role of Dicer in managing collisions is not limited to heterochromatin, but is also important at highly transcribed genes, rDNA and tDNA. These novel Dicer-regulated sites strongly correlates with replication stress, DNA damage and genome instability. A striking example of this is at the subtelomeric rDNA repeats, where Dicer is required to release Pol II to facilitate DNA replication and to prevent homologous recombination, which would otherwise lead to loss of rDNA repeats during mitosis and meiosis. Our results now provide a paradigm for Dicer action at transcription-replication collisions in various genomic contexts. Such collisions have a profound impact in genome and epigenome stability, and contribute to the molecular basis of cancer and ageing.

欢迎各位老师同学积极参加！