Nature Genetics ( IF 31.7 ) Pub Date : 2024-11-08 , DOI: 10.1038/s41588-024-02004-1 Petra Gross
Mammalian pachytene PIWI-interacting RNAs (piRNAs) are expressed during the pachytene stage in spermatocytes with proposed roles in the regulation of meiosis. However, their specific functions and targets remain elusive. In this study, Swathi Arur and colleagues interrogate the function of 21URNAs, the Caenorhabditis elegans piRNAs, and the PIWI homolog prg-1 in the male germline. They show that loss of prg-1 function results in reduced homologous pairing with subsequent defects in crossover formation and chromosome segregation. To determine the targets through which 21URNAs affect meiotic events, the authors sequenced the worm 22G short interfering RNAs (siRNAs) that are generated by 21URNA-mediated silencing. Interestingly, distinct 21URNAs can regulate a single gene in a combinatorial manner. Among the targets identified was Polo-like kinase 3 (PLK-3). Plk-3 mRNA is normally expressed throughout pachytene, but 21URNA activity was found to spatially restrict protein expression to the proliferative region. Accordingly, loss of 21URNAs leads to de-silencing of PLK-3 with defects observed during later meiotic stages. Together, these findings suggest that 21URNAs are a C. elegans equivalent of mammalian pachytene piRNAs and highlight the role of the piRNA pathway in the spatiotemporal regulation of germline genes.
Original reference: Sci. Adv. https://doi.org/10.1126/sciadv.adp0466 (2024)
中文翻译:
piRNA 对种系基因的时空调控
哺乳动物厚壁 PIWI 相互作用 RNA (piRNA) 在厚壁阶段在精母细胞中表达,在减数分裂的调节中发挥作用。然而,它们的具体功能和目标仍然难以捉摸。在这项研究中,Swathi Arur 及其同事询问了雄性种系中 21URNAs、秀丽隐杆线虫 piRNA 和 PIWI 同源物 prg-1 的功能。他们表明,prg-1 功能的丧失导致同源配对减少,随后交叉形成和染色体分离缺陷。为了确定 21URNA 影响减数分裂事件的靶标,作者对 21URNA 介导的沉默产生的蠕虫 22G 短干扰 RNA (siRNA) 进行了测序。有趣的是,不同的 21URNA 可以以组合方式调节单个基因。确定的靶标包括 Polo 样激酶 3 (PLK-3)。Plk-3 mRNA 通常在整个厚层中表达,但发现 21URNA 活性在空间上将蛋白质表达限制在增殖区域。因此,21URNA 的丢失导致 PLK-3 脱沉默,并在减数分裂后期观察到缺陷。总之,这些发现表明 21URNAs 是哺乳动物厚壁 piRNA 的秀丽隐杆线虫等价物,并突出了 piRNA 通路在种系基因时空调控中的作用。
原始参考资料:Sci. Adv.https://doi.org/10.1126/sciadv.adp0466 (2024)