Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Department of Biology, University of North Carolina, Chapel Hill, NC, USA.
Nat Commun. 2021 Mar 3;12(1):1420. doi: 10.1038/s41467-021-21635-0.
In several species, Piwi/piRNA genome silencing defects cause immediate sterility that correlates with transposon expression and transposon-induced genomic instability. In C. elegans, mutations in the Piwi-related gene (prg-1) and other piRNA deficient mutants cause a transgenerational decline in fertility over a period of several generations. Here we show that the sterility of late generation piRNA mutants correlates poorly with increases in DNA damage signaling. Instead, sterile individuals consistently exhibit altered perinuclear germ granules. We show that disruption of germ granules does not activate transposon expression but induces multiple phenotypes found in sterile prg-1 pathway mutants. Furthermore, loss of the germ granule component pgl-1 enhances prg-1 mutant infertility. Environmental restoration of germ granule function for sterile pgl-1 mutants restores their fertility. We propose that Piwi mutant sterility is a reproductive arrest phenotype that is characterized by perturbed germ granule structure and is phenocopied by germ granule dysfunction, independent of genomic instability.
在几种物种中,Piwi/piRNA 基因组沉默缺陷会导致即刻不育,这与转座子表达和转座子诱导的基因组不稳定性相关。在秀丽隐杆线虫中,Piwi 相关基因(prg-1)和其他 piRNA 缺陷突变体的突变会导致几代之后生育能力的代际下降。在这里,我们发现后期世代 piRNA 突变体的不育性与 DNA 损伤信号的增加相关性较差。相反,不育个体始终表现出核周生殖颗粒的改变。我们表明,生殖颗粒的破坏不会激活转座子的表达,但会诱导在不育的 prg-1 途径突变体中发现的多种表型。此外,生殖颗粒成分 pgl-1 的缺失会增强 prg-1 突变体的不育性。恢复不育 pgl-1 突变体生殖颗粒的功能会恢复其生育能力。我们提出,Piwi 突变体的不育是一种生殖阻滞表型,其特征是生殖颗粒结构受到干扰,并表现出生殖颗粒功能障碍的表型,与基因组不稳定性无关。
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