兰州大学机构库 >生命科学学院
MIWI/piRNA在精子发生中调控基因表达的功能机制研究
Alternative TitleThe Roles and Mechanisms of MIWI/piRNA-mediated gene regulation in mouse spermatogenesis
李智彤
Thesis Advisor刘默芳 ; 常民
2015-05-21
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name学士
KeywordMIWI/piRNA HuR 免疫共沉淀 分子克隆
AbstractpiRNA是新近在动物生殖系细胞中发现的一类小分子非编码RNA,因其特异性地与生殖细胞发育必需PIWI家族蛋白相互作用,被命名为PIWI-interacting RNA,简称为piRNA。我们实验室致力于小鼠PIWI蛋白(MIWI)/piRNA在动物精子发生过程中调控基因表达的功能与分子机制研究,前期研究发现,MIWI/piRNA与脱腺苷酸酶CAF1形成piRNA诱导基因沉默复合物(pi-RISC),依赖于piRNA序列的多样性,介导精子发育后期大量mRNA的降解。在精子发生后期,因染色质被高度压缩致转录停止,为后期发育所需基因需提前转录为mRNA ,以翻译抑制状态储存,直至特定精子细胞发育阶段被激活翻译表达,这就是精子形成中广为人知的“转录与翻译解偶联”现象,但目前对于那些处于抑制状态mRNA是如何被翻译激活几乎还一无所知。本论文的研究发现,MIWI通过与一个翻译起始因子复合物亚基及RNA结合蛋白HuR相互作用,在piRNA的指导下,激活了一类单倍体精子细胞中mRNA的翻译,为后期精子细胞发育中的基因表达调控提供了一种全新分子机制,并同时揭示了MIWI/piRNA在小鼠精子发生中的一种新功能。课题研究结果对了解动物生殖细胞发育和配子形成及相关不育症的治疗具有重要的意义。
Other AbstractPIWI-interacting RNAs (piRNAs) are a novel class of small non-coding RNAs that were recently identified in animal germ cells. Our lab has focused on the study of MIWI,one of the PIWI proteins in mice,and piRNAs in regulating gene expression in mouse spermatogenesis.Our previous work has shown that MIWI/piRNA,in complex with deadenylase CAF1, forms piRNA-induced silencing complex (pi-RISC),play an important role in inducing massive mRNA degradation in late stages of spermatogenesis in mouse.A unique feature in late stages of male-germ cell development is the remarkable compaction of sperm chromatin, which results in a drastic inhibition of transcriptional activity at spermiogenesis, the late stages of spermatogenesis. In this regard,the genes that are required for late spermatids and spermatozoa need to be transcribed in advance and stored as repressive mRNAs,and then are translationally activated at a specific stage in haploid spermatid development. This phenomenon,known as "transcription-translation decoupling",is critical important for post-meiotic male germ cell development;however,the mechanisms underlying have remained largely unexplored. Interestingly,our recent work showed that MIWI,in complex with a subunit of the translation initiation complex and a RNA-binding protein HuR,can activate the translation of a specific set of mRNAs in the haploid spermatids in a piRNA-dependent manner.Collectively,our findings have thus provided a novel molecular mechanism regulation in late spermatid development, and revealed a novel function of MIWI/piRNA in mouse spermatogenesis.
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/221942
Collection生命科学学院
Recommended Citation
GB/T 7714
李智彤. MIWI/piRNA在精子发生中调控基因表达的功能机制研究[D]. 兰州. 兰州大学,2015.
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