Telomeric repeat silencing in germ cells is essential for early development in Drosophila.
Telomeric repeat silencing in germ cells is essential for early development in Drosophila.
复制标题
DOI：
10.1093/nar/gkv775
复制
发表时间：
2015-10-15
影响因子：
14.9
通讯作者：
Kalmykova A
中科院分区：
文献类型：
--
作者：
Morgunova V;Akulenko N;Radion E;Olovnikov I;Abramov Y;Olenina LV;Shpiz S;Kopytova DV;Georgieva SG;Kalmykova A
端粒的生殖特异性作用包括染色体末端延长和早期发育阶段染色体的适当分离。尽管端粒在生殖细胞中起着至关重要的作用，但对生殖细胞中端粒的生物学知之甚少。我们分析了果蝇雌性生殖系和早期胚胎的端粒稳态。报道了去腺苷酶复合物Ccr 4-Not在端粒转录监视机制中的一种新的种系特异性功能。Ccr 4-Not复合物组分的耗尽导致生殖细胞中端粒逆转录元件HeT-A的强烈去阻遏，伴随着HeT-A poly（A）尾的延长。转录因子Woc和Trf 2以及RNA结合蛋白Ars 2的功能障碍也导致过度聚腺苷酸化的HeT-A转录物在卵巢中的积累。胚系敲除Ccr 4-Not基因Woc、Trf 2和Ars 2可导致早期胚胎有丝分裂异常，表现为染色体错误分离、中心体功能障碍和纺锤体多极化。此外，所观察到的表型伴随着HeT-A转录物在早期胚胎中心体周围的积累，这表明端粒转录物的过度表达和有丝分裂缺陷之间的假定关系。我们的数据表明，Ccr 4-Not，Woc，Trf 2和Ars 2，不同的调节途径的组件，需要在生殖系中的端粒保护，以保证正常发育。
The germline-specific role of telomeres consists of chromosome end elongation and proper chromosome segregation during early developmental stages. Despite the crucial role of telomeres in germ cells, little is known about telomere biology in the germline. We analyzed telomere homeostasis in the Drosophila female germline and early embryos. A novel germline-specific function of deadenylase complex Ccr4-Not in the telomeric transcript surveillance mechanism is reported. Depletion of Ccr4-Not complex components causes strong derepression of the telomeric retroelement HeT-A in the germ cells, accompanied by elongation of the HeT-A poly(A) tail. Dysfunction of transcription factors Woc and Trf2, as well as RNA-binding protein Ars2, also results in the accumulation of excessively polyadenylated HeT-A transcripts in ovaries. Germline knockdowns of Ccr4-Not components, Woc, Trf2 and Ars2, lead to abnormal mitosis in early embryos, characterized by chromosome missegregation, centrosome dysfunction and spindle multipolarity. Moreover, the observed phenotype is accompanied by the accumulation of HeT-A transcripts around the centrosomes in early embryos, suggesting the putative relationship between overexpression of telomeric transcripts and mitotic defects. Our data demonstrate that Ccr4-Not, Woc, Trf2 and Ars2, components of different regulatory pathways, are required for telomere protection in the germline in order to guarantee normal development.