A microRNA program in the C. elegans hypodermis couples to intestinal mTORC2/PQM-1 signaling to modulate fat transport.
A microRNA program in the C. elegans hypodermis couples to intestinal mTORC2/PQM-1 signaling to modulate fat transport.
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DOI：
10.1101/gad.283895.116
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发表时间：
2016-07-01
影响因子：
10.5
通讯作者：
Ruvkun G
中科院分区：
文献类型：
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作者：
Dowen RH;Breen PC;Tullius T;Conery AL;Ruvkun G
在这项研究中，Dowen等人发现了一个microrna调控的发育时序通路，该通路在秀丽隐杆线虫发育过程中协调肠道脂肪储存向种系的动员。他们的研究结果表明，lin-4和let-7 microRNAs促进mTOR信号传导，从而调节肠道脂肪代谢，从而为microRNAs的新功能提供了见解。在将关键资源用于繁殖之前，动物会整合代谢、发育和环境信息。在秀丽隐杆线虫中，成年动物将脂肪从肠细胞转运到种系以促进繁殖。我们发现了一个microRNA （miRNA）调控的发育时间通路，该通路在皮下组织中起作用，非自主地协调肠道脂肪储存在成年期开始时向种系的动员。这种发育时序通路由lin-4和let-7 mirna控制，参与肠内mTOR信号传导。肠道信号组件是mTORC2特异性的，并与胰岛素途径并行，调节血清/糖皮质激素调节激酶（SGK-1）的活性。令人惊讶的是，SGK-1独立于DAF-16/FoxO起作用；相反，SGK-1促进PQM-1转录因子的细胞质定位，当定位到细胞核时，PQM-1转录因子在转录水平上拮抗肠道脂肪动员。这些结果表明，非细胞自主的发育输入通过参与mTORC2信号来促进脂肪储备从体细胞到种系的组织间运输，从而调节肠道脂肪代谢。
In this study, Dowen et al. identified a microRNA-regulated developmental timing pathway that coordinates the mobilization of intestinal fat stores to the germline during C. elegans development. Their results show that lin-4 and let-7 microRNAs promotes mTOR signaling, which regulates intestinal fat metabolism, thereby providing insight into a novel function for microRNAs. Animals integrate metabolic, developmental, and environmental information before committing key resources to reproduction. In Caenorhabditis elegans, adult animals transport fat from intestinal cells to the germline to promote reproduction. We identified a microRNA (miRNA)-regulated developmental timing pathway that functions in the hypodermis to nonautonomously coordinate the mobilization of intestinal fat stores to the germline upon initiation of adulthood. This developmental timing pathway, which is controlled by the lin-4 and let-7 miRNAs, engages mTOR signaling in the intestine. The intestinal signaling component is specific to mTORC2 and functions in parallel to the insulin pathway to modulate the activity of the serum/glucocorticoid-regulated kinase (SGK-1). Surprisingly, SGK-1 functions independently of DAF-16/FoxO; instead, SGK-1 promotes the cytoplasmic localization of the PQM-1 transcription factor, which antagonizes intestinal fat mobilization at the transcriptional level when localized to the nucleus. These results revealed that a non-cell-autonomous developmental input regulates intestinal fat metabolism by engaging mTORC2 signaling to promote the intertissue transport of fat reserves from the soma to the germline.