The meiotic phosphatase GSP-2/PP1 promotes germline immortality and small RNA-mediated genome silencing
The meiotic phosphatase GSP-2/PP1 promotes germline immortality and small RNA-mediated genome silencing
复制标题
DOI：
10.1371/journal.pgen.1008004
复制
发表时间：
2019-03-01
期刊：
影响因子：
4.5
通讯作者：
Ahmed, Shawn
中科院分区：
文献类型：
--
作者：
Billmyre, Katherine Kretovich;Doebley, Anna-Lisa;Ahmed, Shawn
生殖细胞的不朽或生殖系的跨代维持可以通过有丝分裂或减数分裂生殖细胞中可能发生的机制来促进。本文首次报道了GSP-2 PP1/Glc7磷酸酶促进生殖细胞不朽。众所周知，小rna诱导的基因组沉默可以促进生殖细胞的不朽，我们发现了秀丽隐杆线虫gsp-2的一个功能分离等位基因，该等位基因在生殖细胞不朽中受损，在小rna诱导的基因组沉默和减数分裂而非有丝分裂染色体分离中也存在缺陷。先前的研究表明，GSP-2被LAB-1招募到减数分裂染色体上，这也促进了生殖细胞的不朽。在不育发生时，gsp-2和lab-1突变的成年小鼠在卵母细胞中表现出种系变性、单价性、组蛋白甲基化和组蛋白磷酸化缺陷，这些表型反映了在不育小rna介导的基因组沉默突变体中观察到的表型。我们的数据表明，GSP-2的减数分裂特异性功能将小rna介导的表观基因组沉默与生殖细胞不朽联系在一起。我们还表明，半合子遗传元件的跨代表观基因组沉默需要GSP-2磷酸酶，这表明与小rna的功能联系。考虑到LAB-1在粗线期定位于同源染色体之间的界面，我们假设该界面的小局部不连续性可能以依赖于小rna和GSP-2磷酸酶的方式促进基因组沉默。一个生物体的生殖系被认为是不朽的，因为它有能力产生无限数量的后代。为了保护生殖系的完整性，有机制抑制对基因组或表观基因组的跨代损伤的积累。生殖细胞不朽的丧失可能是由于突变破坏了小rna介导的基因组沉默，这种沉默保护生殖系免受外来遗传元件（如转座子）的侵害。本文首次报道秀丽隐杆线虫蛋白磷酸酶GSP-2在减数分裂过程中促进核心染色体生物学功能，也是生殖细胞不朽所必需的。具体来说，我们确定了gsp-2的部分功能缺失等位基因，该等位基因在减数分裂染色体分离中表现出缺陷，并且在跨代小rna介导的基因组沉默中也表现出功能障碍。我们的结果与果蝇蛋白磷酸酶1在异染色质沉默中的已知作用一致，并指出减数分裂磷酸酶的功能通过促进基因组沉默来响应小rna，从而确保生殖细胞的不朽。
Germ cell immortality, or transgenerational maintenance of the germ line, could be promoted by mechanisms that could occur in either mitotic or meiotic germ cells. Here we report for the first time that the GSP-2 PP1/Glc7 phosphatase promotes germ cell immortality. Small RNA-induced genome silencing is known to promote germ cell immortality, and we identified a separation-of-function allele of C. elegans gsp-2 that is compromised for germ cell immortality and is also defective for small RNA-induced genome silencing and meiotic but not mitotic chromosome segregation. Previous work has shown that GSP-2 is recruited to meiotic chromosomes by LAB-1, which also promoted germ cell immortality. At the generation of sterility, gsp-2 and lab-1 mutant adults displayed germline degeneration, univalents, histone methylation and histone phosphorylation defects in oocytes, phenotypes that mirror those observed in sterile small RNA-mediated genome silencing mutants. Our data suggest that a meiosis-specific function of GSP-2 ties small RNA-mediated silencing of the epigenome to germ cell immortality. We also show that transgenerational epigenomic silencing at hemizygous genetic elements requires the GSP-2 phosphatase, suggesting a functional link to small RNAs. Given that LAB-1 localizes to the interface between homologous chromosomes during pachytene, we hypothesize that small localized discontinuities at this interface could promote genomic silencing in a manner that depends on small RNAs and the GSP-2 phosphatase.Author summary The germ line of an organism is considered immortal in its capacity to give rise to an unlimited number of future generations. To protect the integrity of the germ line, mechanisms act to suppress the accumulation of transgenerational damage to the genome or epigenome. Loss of germ cell immortality can result from mutations that disrupt small RNA-mediated genome silencing, which protects the germ line from foreign genetic elements such as transposons. Here we report for the first time that the C. elegans protein phosphatase GSP-2 that promotes core chromosome biology functions during meiosis is also required for germ cell immortality. Specifically, we identified a partial loss-of-function allele of gsp-2 that exhibits defects in meiotic chromosome segregation and that is also dysfunctional for transgenerational small RNA-mediated genome silencing. Our results are consistent with a known role of Drosophila Protein Phosphatase 1 in heterochromatin silencing, and point to a meiotic phosphatase function that ensures germ cell immortality by promoting genomic silencing in response to small RNAs.