ï»?!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Transitional//EN" "http://www.w3.org/TR/xhtml1/DTD/xhtml1-transitional.dtd"> 【科学前沿】生殖所袁水桥课题组在生殖细胞发育领域取得新成果-华中科技大学同济医学é™?/title><META Name="keywords" Content="华中科技大学同济医学é™?综合新闻,科学,学前,前沿,生殖,课题ç»?课题,在生,生殖细胞,细胞,发育,领域,取得,成果" /> <META Name="description" Content="6æœ?3日,生殖健康研究所袁水桥教授课题组在自然子刊Nature Communications杂志上在线发表题为“hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells”的研究论文。该论文首次揭示了RNA结合蛋白hnRNPH1在小鼠生殖细胞(包括雄性与雌性生殖细胞)发育中的重要作用,并发现hnRNPH1通过募集剪接因子PTBP2和SRSF3以调控生殖细胞发育相关靶基因的可变剪接,从而维持生精细胞和卵母细胞的正常发育及åŠ?.." /> <meta name="description" content="《中国医疗卫生事业发展报å‘?016》在同济医学院发å¸?华中科技大学同济医学é™?武汉同济医学é™?同济医学é™? /> <link href="../../dfiles/11375/css/public.css" rel="stylesheet" type="text/css" /><link href="../../dfiles/11375/css/second.css" rel="stylesheet" type="text/css" /><link href="../../dfiles/11375/css/main.css" rel="stylesheet" /> <link href="../../dfiles/11375/css/iconfont.css" rel="stylesheet" /> <script src="../../dfiles/11375/js/batxk.js"></script> <style type="text/css"> /*分页样式*/ .paginator { font-size:12px;padding:2px 10px 2px 0; 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line-height: 2em; text-indent: 2em;"><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;"><br></span></p> <p style="text-align: justify; line-height: 2em; text-indent: 2em;"><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">6</span><span style="color: black; font-family: 宋体; font-size: 16px;">æœ?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">23</span><span style="color: black; font-family: 宋体; font-size: 16px;">日,生殖健康研究所袁水桥教授课题组在自然子åˆ?/span><strong><em><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">Nature Communications</span></em></strong><span style="color: black; font-family: 宋体; font-size: 16px;">杂志上在线发表题为â€?/span><em><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells</span></em><span style="color: black; font-family: 宋体; font-size: 16px;">”的研究论文。该论文首次揭示äº?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">RNA</span><span style="color: black; font-family: 宋体; font-size: 16px;">结合蛋白</span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">hnRNPH1</span><span style="color: black; font-family: 宋体; font-size: 16px;">在小鼠生殖细胞(包括雄性与雌性生殖细胞)发育中的重要作用,并发现</span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">hnRNPH1</span><span style="color: black; font-family: 宋体; font-size: 16px;">通过募集剪接因子</span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">PTBP2</span><span style="color: black; font-family: 宋体; font-size: 16px;">å’?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">SRSF3</span><span style="color: black; font-family: 宋体; font-size: 16px;">以调控生殖细胞发育相关靶基因的可变剪接,从而维持生精细胞和卵母细胞的正常发育及功能ã€?/span></p> <p style="text-align: center; line-height: 2em; text-indent: 0em;"> </p> <p style="text-align: center;"><img width="500" height="223" src="/__local/0/F2/43/DCB32C32D9A47AA1470D5514421_1B39EFBF_52E70.jpg" vwidth=" 568px" vheight=" 239px" vurl="/_vsl/0F243DCB32C32D9A47AA1470D5514421/1B39EFBF/52E70" vsbhref="vurl" orisrc="/__local/0/F2/43/DCB32C32D9A47AA1470D5514421_1B39EFBF_52E70.jpg" class="img_vsb_content" style="width: 568px; height: 239px;"></p> <p style="text-align: justify; line-height: 2em; text-indent: 2em;"> </p> <p style="text-align: justify; line-height: 2em; text-indent: 2em;"><span style="color: black; font-family: 宋体; font-size: 16px;">可变剪接(又ç§?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">Pre-mRNA</span><span style="color: black; font-family: 宋体; font-size: 16px;">选择性剪接)的协同调控对生殖细胞发育至关重要。在精子发生过程中,可变剪接在维持转录组和蛋白质组多样性等方面起重要作用。大多数参与精子发生的基因都被转录并加工成多个转录本,最终翻译成不同功能的蛋白质,这对于睾丸</span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">/</span><span style="color: black; font-family: 宋体; font-size: 16px;">卵巢等高度复杂的器官的发育尤为关键。然而,在生殖细胞发育过程中调控可变剪接的分子机制仍知之甚少。可变剪接通常由剪接因子介导,而剪接体的组装和剪接位点的选择å?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">RNA</span><span style="color: black; font-family: 宋体; font-size: 16px;">结合蛋白调控。尽管一些在精子发生过程中起关键作用çš?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">RNA</span><span style="color: black; font-family: 宋体; font-size: 16px;">结合蛋白或剪接因子(å¦?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">PTBP2</span><span style="color: black; font-family: 宋体; font-size: 16px;">)被陆续发现,但它们是否在调控可变剪接方面具有协同作用,目前还不清楚ã€?/span></p> <p style="text-align: justify; line-height: 2em; text-indent: 2em;"><span style="color: black; font-family: 宋体; font-size: 16px;"><br></span></p> <p style="text-align: center; line-height: 2em; text-indent: 0em;"><span style="color: black; font-family: 宋体; font-size: 16px;"></span></p> <p style="text-align: center;"><img width="500" src="/__local/6/21/A0/1AEFF3C8D9110B208825617948A_22D245C8_54B58.jpg" vwidth="500" vheight="" vurl="/_vsl/621A01AEFF3C8D9110B208825617948A/22D245C8/54B58" vsbhref="vurl" orisrc="/__local/6/21/A0/1AEFF3C8D9110B208825617948A_22D245C8_54B58.jpg" class="img_vsb_content"></p> <p style="text-align: center; line-height: 2em; text-indent: 0em;"><br></p> <p style="text-align: justify; line-height: 2em; text-indent: 2em;"><span style="color: black; font-family: 宋体; font-size: 16px;">袁水桥课题组在前期的研究基础上,发现核不均一</span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">RNA</span><span style="color: black; font-family: 宋体; font-size: 16px;">结合蛋白â€?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">hnRNPH1</span><span style="color: black; font-family: 宋体; font-size: 16px;">在粗线期精母细胞、圆形精子细胞以及卵母细胞中高表达。接着课题组利用免疫共沉淀</span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">-</span><span style="color: black; font-family: 宋体; font-size: 16px;">质谱串联ï¼?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">IP-MS</span><span style="color: black; font-family: 宋体; font-size: 16px;">)技术发çŽ?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">hnRNPH1</span><span style="color: black; font-family: 宋体; font-size: 16px;">与剪接调节因å­?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">PTBP2</span><span style="color: black; font-family: 宋体; font-size: 16px;">å’?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">SRSF3</span><span style="color: black; font-family: 宋体; font-size: 16px;">互作,并通过</span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">CO-IP</span><span style="color: black; font-family: 宋体; font-size: 16px;">实验探索了它们之间的互作结构域。这些结果提ç¤?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">hnNPH1</span><span style="color: black; font-family: 宋体; font-size: 16px;">可能在精子发生过程中参与调控可变剪接。此后,利用条件性基因敲除手段,在小鼠生殖细胞中特异敲除</span><em><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">Hnrnph1</span></em><span style="color: black; font-family: 宋体; font-size: 16px;">基因,通过分析敲除小鼠的生殖表型并结合</span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">RNA-seq</span><span style="color: black; font-family: 宋体; font-size: 16px;">高通量测序技术,发现特异敲除</span><em><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">Hnrnph1</span></em><span style="color: black; font-family: 宋体; font-size: 16px;">导致精母细胞和圆形精子中许多异常的剪接事件发生,从而影响减数分裂和生殖细胞</span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">-</span><span style="color: black; font-family: 宋体; font-size: 16px;">支持细胞通讯相关基因的表达,造成染色体联会异常以及生殖细胞与支持细胞之间的通讯受损,最终导致雄性小鼠不育。有趣的是,研究还发çŽ?/span><em><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">Hnrnph1</span></em><span style="color: black; font-family: 宋体; font-size: 16px;">特异性敲除的雌性小鼠同样不育,</span><em><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">Hnrnph1</span></em><span style="color: black; font-family: 宋体; font-size: 16px;">敲除的卵母细胞表现出与雄性生殖细胞相似的表型,即减数分裂异常以及卵母细胞与颗粒细胞之间通讯受阻。接着该课题组利用</span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">RIP-seq</span><span style="color: black; font-family: 宋体; font-size: 16px;">技术证å®?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">hnRNPH1</span><span style="color: black; font-family: 宋体; font-size: 16px;">能够直接结合许多关键靶基因的</span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">mRNA</span><span style="color: black; font-family: 宋体; font-size: 16px;">。进一步研究发现,</span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">hnRNPH1</span><span style="color: black; font-family: 宋体; font-size: 16px;">同样能够在卵巢中招募剪接因子</span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">PTBP2</span><span style="color: black; font-family: 宋体; font-size: 16px;">å’?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">SRSF3</span><span style="color: black; font-family: 宋体; font-size: 16px;">,并协同调控生殖细胞发育所需关键基因的可变剪接。总之,该研究首次揭示äº?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">hnRNPH1</span><span style="color: black; font-family: 宋体; font-size: 16px;">在生殖细胞发育中的重要作用,并提出了</span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">RNA</span><span style="color: black; font-family: 宋体; font-size: 16px;">结合蛋白和不同剪接因子在精子发生和卵母细胞发育过程中协同调控可变剪接的分子机制假说(å›?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;">1</span><span style="color: black; font-family: 宋体; font-size: 16px;">)ã€?/span></p> <p style="text-align: justify; line-height: 2em; text-indent: 2em;"><span style="color: black; font-family: 宋体; font-size: 16px;"><br></span></p> <p style="text-align: center; line-height: 2em; text-indent: 0em;"><span style="color: black; font-family: 宋体; font-size: 16px;"></span></p> <p style="text-align: center;"><img width="500" src="/__local/B/26/4D/0F04731D8E5338499D1BBE88AC0_7A20A788_13A49.jpg" vwidth="500" vheight="" vurl="/_vsl/B264D0F04731D8E5338499D1BBE88AC0/7A20A788/13A49" vsbhref="vurl" orisrc="/__local/D/B9/2A/7397D464833102BB33013A486A8_2FB7C8B8_DB3FE.jpg" class="img_vsb_content"></p> <p style="text-align: center;"><span style="color: black; font-family: 宋体; font-size: 16px;"><span lang="EN-US" style="background: white; color: black; letter-spacing: 0px; font-family: times new roman,serif;"><span style="background: white; color: black; letter-spacing: 0px; font-family: 宋体; font-size: 14px;">å›?/span><span lang="EN-US" style="background: white; color: black; letter-spacing: 0px; font-family: times new roman,serif; font-size: 14px;">1. hnRNPH1</span><span style="background: white; color: black; letter-spacing: 0px; font-family: 宋体; font-size: 14px;">调控可变剪接和生殖细胞发育的模式图ã€?/span></span></span></p> <p><span style="color: black; font-family: 宋体; font-size: 16px;"><span lang="EN-US" style="background: white; color: black; letter-spacing: 0px; font-family: times new roman,serif;"><span style="background: white; color: black; letter-spacing: 0px; font-family: 宋体; font-size: 14px;"><br></span></span></span></p> <p><span style="color: black; font-family: 宋体; font-size: 16px;"><span lang="EN-US" style="background: white; color: black; letter-spacing: 0px; font-family: times new roman,serif;"><span style="background: white; color: black; letter-spacing: 0px; font-family: 宋体; font-size: 14px;"></span></span></span></p> <p style="text-align: justify; line-height: 2em; text-indent: 2em;"><span lang="EN-US" style="background: white; color: black; letter-spacing: 0px; font-family: times new roman,serif;"> </span></p> <p style="text-align: justify; line-height: 2em; text-indent: 2em; -ms-text-justify: inter-ideograph;"><span style="font-size: 16px;"><span style="background: white; color: black; letter-spacing: 0px; font-family: 宋体;">华中科技大学同济医学院生殖健康研究所为本研究论文的第一完成单位。生殖健康研究所博士后丰胜磊、硕士生李金梅为该论文的共同第一作者,袁水桥教授为唯一独立通讯作者。该研究得到了国家自然科学基金面上项目和深圳华中科技大学研究é™?/span><span lang="EN-US" style="background: white; color: black; letter-spacing: 0px; font-family: times new roman,serif;">-</span><span style="background: white; color: black; letter-spacing: 0px; font-family: 宋体;">深圳科技创新委员会重点项目的资助。该研究成果是袁水桥教授课题组在精子发生与男性不育调控领域取得的又一项重要突破ã€?/span></span></p> <p style="text-align: justify; line-height: 2em; text-indent: 2em;"><sub> </sub></p> <p style="text-align: justify; line-height: 2em; text-indent: 2em;"><sub> </sub></p> <p style="text-align: justify; line-height: 2em; text-indent: 2em;"><sub> </sub></p> <p style="text-align: justify; line-height: 2em; text-indent: 2em;"><span style="background: white; color: black; letter-spacing: 0px; font-family: 宋体; font-size: 16px;">原文链接ï¼?/span><span lang="EN-US" style="color: black; font-family: times new roman,serif; font-size: 16px;"><a ><span style="color: rgb(5, 99, 193);">https://www.nature.com/articles/s41467-022-31364-7</span></a></span></p> <p> </p> <p> </p> </div></div> </form> </div> </div> </div> <script src="../../dfiles/11375/js/batxkx.js" type="text/javascript"></script> <script src="../../dfiles/11375/js/wwwzzjsnet.js" type="text/javascript"></script> <link href="../../dfiles/11375/main/css/iconfont.css" rel="stylesheet" /> <script type="text/javascript"> <!-- $(function () { // 鼠标移动到list的div上的时候list div不会被隐è—? $(".weixin").hover(function () { $(".con").show(); 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