2017.09.15 Study and screen microRNA function using gene editing nuclease
题 目: Study and screen microRNA function using gene editing nuclease TALEN or crispr/Cas9
报告人: Ren-Jang Lin
Professor, Department of Molecular and Cellular Biology, City of Hope Beckman Research Institute
Associate Dean for Curriculum Development, City of Hope Irell & Manella Graduate School of Biological Sciences
时 间: 2017年9月15日(周五)14:00-15:00
地 点: 北京大学老化学楼东配楼101报告厅
主持人: 来鲁华 教授
MicroRNAs regulate genes important for cellular development, differentiation, proliferation, and apoptosis. The values of microRNAs as cancer markers and targets are widely recognized. To facilitate functional study of microRNA, we constructed sequence-specific nucleases such as TALEN and crispr/Cas9 to target a particular microRNA or an entire set of microRNAs. For example, we used TALEN to knockout miR-21 and found cells lacking miR-21 were less transformed, more sensitive to genotoxic drugs, and increased in expression of genes involved in extracellular matrix interactions. We have also designed a crispr/Cas9 library to target 85% of all annotated human microRNAs with improved specificity than existing ones. This genome-wide library was used in HeLa cells to identify microRNA important for cell growth. One of the microRNAs identified is miR-151a, which is found to overexpress in cervical cancer specimens but whose molecular mechanism in cervical cancer is not known. We validated the pro-growth characteristics by generating miR-151a mutant cell clones and RNA-Seq analysis revealed genes/pathways that may be important for cervical cancer. Our microRNA-targeting crispr library is also being used to screen for microRNA associated with HIV latency and microRNA involved in retinoic acid induced hematopoietic cell differentiation.
Ren-Jang Lin is a full professor of Department of Molecular And Cellular Biology at the City of Hope Beckman Research Institute, and the associate dean of Curriculum Development at the City of Hope Graduate School.
Prof. Ren-Jang Lin has a broad background in the biochemistry and genomics of post-transcriptional gene regulation, with expertise in RNA splicing and the spliceosome, ribonucleoprotein-remodeling helicases, RNA-binding proteins, and microRNA. He has published 50 peer-reviewed research articles in journals such as Nature, Cell, PNAS, Genes & Development, EMBO Journal, Cancer Research, and so on, and edited two books on RNA-Protein Interaction and written several book chapters. He has initiated and managed research projects in the investigation of RNA splicing, the spliceosome, microRNA, and cancer, with grants from NIH, the Welch Foundation, Leukemia Society, and CIRM (California Institute of Regenerative Medicine).