Murchison Elizabeth P, Stein Paula, Xuan Zhenyu, Pan Hua, Zhang Michael Q, Schultz Richard M, Hannon Gregory J
Cold Spring Harbor Laboratory, Watson School of Biological Sciences and Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA.
Genes Dev. 2007 Mar 15;21(6):682-93. doi: 10.1101/gad.1521307.
Dicer is an essential component of RNA interference (RNAi) pathways, which have broad functions in gene regulation and genome organization. Probing the consequences of tissue-restricted Dicer loss in mice indicates a critical role for Dicer during meiosis in the female germline. Mouse oocytes lacking Dicer arrest in meiosis I with multiple disorganized spindles and severe chromosome congression defects. Oogenesis and early development are times of significant post-transcriptional regulation, with controlled mRNA storage, translation, and degradation. Our results suggest that Dicer is essential for turnover of a substantial subset of maternal transcripts that are normally lost during oocyte maturation. Furthermore, we find evidence that transposon-derived sequence elements may contribute to the metabolism of maternal transcripts through a Dicer-dependent pathway. Our studies identify Dicer as central to a regulatory network that controls oocyte gene expression programs and that promotes genomic integrity in a cell type notoriously susceptible to aneuploidy.
Dicer是RNA干扰(RNAi)途径的重要组成部分,RNAi途径在基因调控和基因组组织中具有广泛功能。对小鼠组织特异性Dicer缺失后果的探究表明,Dicer在雌性生殖系减数分裂过程中起关键作用。缺乏Dicer的小鼠卵母细胞在减数分裂I期停滞,伴有多个紊乱的纺锤体和严重的染色体排列缺陷。卵子发生和早期发育是转录后调控的重要时期,涉及mRNA的储存、翻译和降解的控制。我们的结果表明,Dicer对于母源转录本的大量子集的周转至关重要,这些转录本通常在卵母细胞成熟过程中丢失。此外,我们发现证据表明转座子衍生的序列元件可能通过Dicer依赖途径参与母源转录本的代谢。我们的研究确定Dicer是控制卵母细胞基因表达程序并促进基因组完整性的调控网络的核心,而该细胞类型极易发生非整倍体。