PIWI相互作用RNA(piRNA)通路控制转座子在动物生殖细胞中的表达,从而确保几代人的基因组稳定性。在果蝇中,piRNAs是通过母体谱系代际遗传的,这已经证明了在piRNA来源基因座的规范以及在女儿的生殖细胞中I-和P-元件的沉默中的重要性。母体遗传的Piwi蛋白在合子基因组激活之前进入早期胚胎的体细胞核,并在其中持续完成胚胎发育所需时间的大约一半。探讨piRNA通路在胚胎体细胞中的作用,我们创造了一种条件不稳定的Piwi蛋白.这使母本沉积的Piwi能够在30分钟内从新产下的胚胎中清除,并且远远早于合子转录的激活。随着时间的推移检查RNA和蛋白质谱,以及与H3K9me3沉积模式的相关性,提示母体沉积的Piwi在减弱发育中胚胎体细胞中合子转座子表达中的作用。特别是,靶向roo的piRNAs的强烈沉积,表达主要限于胚胎发育的元素,导致在活跃的roo插入处沉积瞬时异色标记。我们假设Roo,一个非常成功的移动元素,可能已经采取了在胚胎体细胞中表达的生活方式来逃避生殖细胞的沉默。
保持DNA的完整性,它编码了生命所需的所有指令,对于确保一个物种的生存至关重要,特别是当遗传信息跨代转移时。DNA,然而,包含自私,移动元素,称为转座子,在基因组周围移动,因此他们的绰号是“跳跃基因”。他们的运动,这些元素也在基因组中繁殖的过程,如果转座子恰好落在基因中间,就会混淆生物体的DNA,产生一个突变,使基因失活。转座子也与癌症的发展有关,这是一组由积累的基因突变驱动的疾病。动物已经进化出各种保护其DNA免受转座子侵害的方法。这些在卵细胞和精子发育中特别重要,统称为生殖细胞。这些细胞可以产生小的RNA片段,类似于DNA的分子,能够识别和解除转座子。虽然已知这些小RNA有效保护成年性腺免受DNA损伤,目前还不清楚如何保护生命初期形成的生殖细胞。了解更多,法布里等人。使用了基因测序的组合,蛋白质结合和成像研究,以观察小RNA的活性,称为piRNAs,从母亲传给她的后代。通过研究果蝇胚胎的基因表达水平,法布里等人。表明某些转座子在胚胎发育的最初几个小时变得高度活跃,对DNA完整性构成潜在威胁。实验还确定了胚胎中控制转座子的活性机制的明确迹象,该机制类似于成年生殖细胞已知的小RNA系统。法布里等人。从胚胎中去除piRNA,发现没有piRNA,转座子更活跃。这表明这些小RNA在早期发育中控制转座子中的直接作用,并证明了早期胚胎中的母系遗传防御系统。这项研究为苍蝇胚胎中转座子的控制提供了见解。需要更多的研究来发现这些胚胎机制在其他动物中是否保守,包括人类。研究防止DNA损伤和保护我们基因组的内在机制,在时间上,帮助确定可能治疗和预防涉及基因突变的疾病的新方法。
The PIWI-interacting RNA (piRNA) pathway controls transposon expression in animal germ cells, thereby ensuring genome stability over generations. In Drosophila, piRNAs are intergenerationally inherited through the maternal lineage, and this has demonstrated importance in the specification of piRNA source loci and in silencing of I- and P-elements in the germ cells of daughters. Maternally inherited Piwi protein enters somatic nuclei in early embryos prior to zygotic genome activation and persists therein for roughly half of the time required to complete embryonic development. To investigate the role of the piRNA pathway in the embryonic soma, we created a conditionally unstable Piwi protein. This enabled maternally deposited Piwi to be cleared from newly laid embryos within 30 min and well ahead of the activation of zygotic transcription. Examination of RNA and protein profiles over time, and correlation with patterns of H3K9me3 deposition, suggests a role for maternally deposited Piwi in attenuating zygotic transposon expression in somatic cells of the developing embryo. In particular, robust deposition of piRNAs targeting roo, an element whose expression is mainly restricted to embryonic development, results in the deposition of transient heterochromatic marks at active roo insertions. We hypothesize that roo, an extremely successful mobile element, may have adopted a lifestyle of expression in the embryonic soma to evade silencing in germ cells.
Maintaining the integrity of DNA, which encodes all of the instructions necessary for life, is essential for ensuring the survival of a species, especially when genetic information is transferred across generations. DNA, however, contains selfish, mobile elements, called transposons, that move around the genome, hence their nickname ‘jumping genes’. Their movement, a process by which these elements also multiply within genomes, can muddle an organism’s DNA if the transposon happens to land in the middle of a gene, creating a mutation which renders the gene inactive. Transposons have also been linked to the development of cancer, which is a group of diseases driven by accumulating genetic mutations. Animals have evolved various ways of protecting their DNA against transposons. These are especially important in developing egg cells and sperm, known collectively as germ cells. These cells can produce small fragments of RNA, a molecule similar to DNA, which are able to identify and disarm transposons. While it is known that these small RNAs effectively protect adult gonads from DNA damage, it has been unclear how germ cells formed during the beginning of life are protected. To find out more, Fabry et al. used a combination of genetic sequencing, protein binding and imaging studies to look at the activity of small RNAs, called piRNAs, which are passed on from the mother to her progeny. By studying the gene expression levels in fruit fly embryos, Fabry et al. showed that certain transposons become highly active in the first few hours of embryo development, posing a potential threat to DNA integrity. The experiments also identified clear signs in the embryos of an active mechanism for controlling transposons that resembles the small RNA system known from adult germ cells. Fabry et al. removed the piRNAs from the embryos and found that without piRNAs, transposons were more active. This indicates a direct role of these small RNAs in controlling transposons in early development and evidence for a maternally inherited defence system in early embryos. This study provides insights into the control of transposons in fly embryos. More research is needed to find out whether these embryonic mechanisms are conserved in other animals, including humans. Studying the intrinsic mechanisms that prevent DNA damage and protect our genome could, in time, help to identify new approaches to possibly treat and prevent diseases involving genetic mutations.