题 目: The function of MIWI/piRNA complex is highly regulated during mouse spermiogenesis
主讲人:刘默芳 研究员
主持人:翁杰敏 教 授
时 间:10月22日 14:00
地 点:闵行校区生科院534报告厅
报告人简介：
刘默芳，博士，现任中科院上海生化与细胞所研究组长（PI）、研究员、博士生导师。分别于1991年、1994年在华东理工大学获学士、硕士学位，2000年在中科院上海生物化学研究所获博士学位。分别于2000 -2005年、2005-2006年在美国国家健康研究院癌症研究所 (National Cancer Institute, NIH)博士后研究、约翰霍浦金斯医学院遗传和分子生物学系任研究助理。2006-至今，中科院上海生化细胞所，先后担任co-PI、RNA研究技术平台主任、研究组长。2013年入选国家杰出青年科学基金获得者。研究方向：非编码RNA在癌症发生和精子发生中的功能机制。研究组主要兴趣在于了解小分子非编码RNA的功能和作用机制，开展了miRNA在癌症发生中的功能机制、piRNA在哺乳动物精子发生中的功能机制等两方面的研究。
报告内容简介：
In mice, piRNAs are expressed in two distinct phases during male germ cell development and are respectively termed as pre-pachytene and pachytene piRNAs. Pre-pachytene piRNAs, which are enriched in transposon sequences and co-expressed with MIWI2 and/or MILI in early stages of spermatogenesis, are primarily involved in de novo DNA methylation in fetal and perinatal male germ cells. The function of pachytene piRNAs, which are strongly induced mainly from non-transposon intergenic regions and largely co-expressed with MIWI in pachytene spermatocytes and post-meiotic spermatids, remained elusive. Our recent study indicated that MIWI, in complex with pachytene piRNAs and a deadenylase CAF1, assembles the piRNA-Induced Silencing Complex (pi-RISC) in elongating spermatids, which mediates the decay of a large population of mRNAs in these cells. Our findings elucidate a key function of pachytene piRNAs in development, which provide an important mechanism responsible for the elimination of mRNAs in late stages of spermiogenesis. Intriguingly, we found that at a later stage of spermiogenesis, piRNAs trigger MIWI ubiquitination by a multi-subunit E3 ubiquitin ligase the Anaphase Promoting Complex/Cyclosome (APC/C), thus leading to the degradation of MIWI through the Ubiquitin-26S proteasome pathway. Moreover, such piRNA-triggered MIWI destruction leads to piRNA elimination, thereby suggesting a feed-forward mechanism for coordinated removal of the MIWI/piRNA machinery after it fulfills all of its function for spermatogenesis. Importantly, the proper removal of MIWI/piRNA is essential for sperm maturation. Together, our results suggest that the function of MIWI/piRNA complex is highly regulated during mouse spermiogenesis.
