长非编码 RNA lep-5 通过使 LIN-28 失稳来促进幼年向成年的过渡。
The Long Non-Coding RNA lep-5 Promotes the Juvenile-to-Adult Transition by Destabilizing LIN-28.
机构信息
Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003, USA.
Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003, USA; Department of Applied Mathematics and Statistics, Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY 11794-5252, USA.
出版信息
Dev Cell. 2019 May 20;49(4):542-555.e9. doi: 10.1016/j.devcel.2019.03.003. Epub 2019 Apr 4.
Biological roles for most long non-coding RNAs (lncRNAs) remain mysterious. Here, using forward genetics, we identify lep-5, a lncRNA acting in the C. elegans heterochronic (developmental timing) pathway. Loss of lep-5 delays hypodermal maturation and male tail tip morphogenesis (TTM), hallmarks of the juvenile-to-adult transition. We find that lep-5 is a ∼600 nt cytoplasmic RNA that is conserved across Caenorhabditis and possesses three essential secondary structure motifs but no essential open reading frames. lep-5 expression is temporally controlled, peaking prior to TTM onset. Like the Makorin LEP-2, lep-5 facilitates the degradation of LIN-28, a conserved miRNA regulator specifying the juvenile state. Both LIN-28 and LEP-2 associate with lep-5 in vivo, suggesting that lep-5 directly regulates LIN-28 stability and may function as an RNA scaffold. These studies identify a key biological role for a lncRNA: by regulating protein stability, it provides a temporal cue to facilitate the juvenile-to-adult transition.
大多数长非编码 RNA（lncRNA）的生物学功能仍然是个谜。在这里，我们采用正向遗传学的方法，鉴定了 lep-5，这是一个在秀丽隐杆线虫的时序（发育定时）途径中起作用的 lncRNA。lep-5 的缺失会延迟真皮的成熟和雄性尾尖形态发生（TTM），这是从幼虫到成虫过渡的标志。我们发现 lep-5 是一种约 600 个核苷酸的细胞质 RNA，在秀丽隐杆线虫中是保守的，具有三个必需的二级结构基序，但没有必需的开放阅读框。lep-5 的表达是时间控制的，在 TTM 开始之前达到峰值。像 Makorin LEP-2 一样，lep-5 促进了 LIN-28 的降解，LIN-28 是一种保守的 miRNA 调节剂，指定了幼虫状态。LIN-28 和 LEP-2 在体内都与 lep-5 结合，这表明 lep-5 直接调节 LIN-28 的稳定性，并可能作为 RNA 支架发挥作用。这些研究确定了 lncRNA 的一个关键生物学作用：通过调节蛋白质稳定性，它提供了一个时间线索，促进了从幼虫到成虫的过渡。
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