Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island 02912, USA.
Nat Commun. 2016 Dec 21;7:13856. doi: 10.1038/ncomms13856.
In gonadal tissues, the Piwi-interacting (piRNA) pathway preserves genomic integrity by employing 23-29 nucleotide (nt) small RNAs complexed with argonaute proteins to suppress parasitic mobile sequences of DNA called transposable elements (TEs). Although recent evidence suggests that the piRNA pathway may be present in select somatic cells outside the gonads, the role of a non-gonadal somatic piRNA pathway is not well characterized. Here we report a functional somatic piRNA pathway in the adult Drosophila fat body including the presence of the piRNA effector protein Piwi and canonical 23-29 nt long TE-mapping piRNAs. The piwi mutants exhibit depletion of fat body piRNAs, increased TE mobilization, increased levels of DNA damage and reduced lipid stores. These mutants are starvation sensitive, immunologically compromised and short-lived, all phenotypes associated with compromised fat body function. These findings demonstrate the presence of a functional non-gonadal somatic piRNA pathway in the adult fat body that affects normal metabolism and overall organismal health.
在性腺组织中,Piwi 相互作用(piRNA)途径通过利用 23-29 个核苷酸(nt)的小 RNA 与 Argonaute 蛋白复合物来抑制称为转座元件(TEs)的寄生 DNA 移动序列,从而保持基因组完整性。尽管最近的证据表明,piRNA 途径可能存在于性腺外的某些体细胞中,但非性腺体 piRNA 途径的作用尚未得到很好的描述。在这里,我们报道了成年果蝇脂肪体中存在功能性的体 piRNA 途径,包括 piRNA 效应蛋白 Piwi 和典型的 23-29 nt 长的 TE 映射 piRNAs 的存在。piwi 突变体表现出脂肪体 piRNA 的耗竭、TE 转座增加、DNA 损伤水平增加和脂质储存减少。这些突变体对饥饿敏感、免疫受损和寿命缩短,所有这些表型都与脂肪体功能受损有关。这些发现表明,成年脂肪体中存在一种功能性的非性腺体体细胞 piRNA 途径,它影响正常的新陈代谢和整体机体健康。