The Makorin lep-2 and the lncRNA lep-5 regulate lin-28 to schedule sexual maturation of the C. elegans nervous system
The Makorin lep-2 and the lncRNA lep-5 regulate lin-28 to schedule sexual maturation of the C. elegans nervous system
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DOI：
10.7554/elife.43660
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发表时间：
2019-07-02
期刊：
影响因子：
7.7
通讯作者：
Portman, Douglas S.
中科院分区：
文献类型：
--
作者：
Lawson, Hannah;Vuong, Edward;Portman, Douglas S.
性成熟必须在一个受控的发育时间表上发生。在哺乳动物中，Makorin 3（MKRN 3）和miRNA调节因子LIN 28 A/B是这一过程的关键调节因子，但它们如何起作用尚不清楚。In C.在线虫中，神经系统的性成熟包括有丝分裂后神经元的功能重塑和成年特异性行为的开始。在这里，我们发现lin-28-let-7轴（“异时路径”）决定了这些事件的发生时间。lin-28上游的Makorin lep-2和lncRNA lep-5调控成熟的细胞自主性，表明分布的时钟，而不是一个中央定时器，协调性分化的C。神经系统。人MKRN 3的过表达延迟了C. elegans性成熟，提示Makorin功能的保守性。这些研究揭示了Makorin和lncRNA在性分化时间中的作用;此外，它们证明了lin-28-let-7系统在控制神经系统功能成熟中的深度保守性。
Sexual maturation must occur on a controlled developmental schedule. In mammals, Makorin3 (MKRN3) and the miRNA regulators LIN28A/B are key regulators of this process, but how they act is unclear. In C. elegans, sexual maturation of the nervous system includes the functional remodeling of postmitotic neurons and the onset of adult-specific behaviors. Here, we find that the lin-28-let-7 axis (the 'heterochronic pathway') determines the timing of these events. Upstream of lin-28, the Makorin lep-2 and the lncRNA lep-5 regulate maturation cell-autonomously, indicating that distributed clocks, not a central timer, coordinate sexual differentiation of the C. elegans nervous system. Overexpression of human MKRN3 delays aspects of C. elegans sexual maturation, suggesting the conservation of Makorin function. These studies reveal roles for a Makorin and a lncRNA in timing of sexual differentiation; moreover, they demonstrate deep conservation of the lin-28-let-7 system in controlling the functional maturation of the nervous system.