Ríos-Barrera Luis Daniel, Gutiérrez-Pérez Irene, Domínguez María, Riesgo-Escovar Juan Rafael
Instituto de Neurobiología, Universidad Nacional Autónoma de México, campus UNAM Juriquilla, Querétaro, México.
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Campus de San Juan, Sant Joan d'Alacant, Alicante, España.
PLoS Genet. 2015 Feb 24;11(2):e1004927. doi: 10.1371/journal.pgen.1004927. eCollection 2015.
Dorsal closure is an epithelial remodeling process taking place during Drosophila embryogenesis. JNK signaling coordinates dorsal closure. We identify and characterize acal as a novel negative dorsal closure regulator. acal represents a new level of JNK regulation. The acal locus codes for a conserved, long, non-coding, nuclear RNA. Long non-coding RNAs are an abundant and diverse class of gene regulators. Mutations in acal are lethal. acal mRNA expression is dynamic and is processed into a collection of 50 to 120 bp fragments. We show that acal lies downstream of raw, a pioneer protein, helping explain part of raw functions, and interacts genetically with Polycomb. acal functions in trans regulating mRNA expression of two genes involved in JNK signaling and dorsal closure: Connector of kinase to AP1 (Cka) and anterior open (aop). Cka is a conserved scaffold protein that brings together JNK and Jun, and aop is a transcription factor. Misregulation of Cka and aop can account for dorsal closure phenotypes in acal mutants.
背侧闭合是果蝇胚胎发育过程中发生的一种上皮重塑过程。JNK信号通路协调背侧闭合。我们鉴定并表征了Acal作为一种新型的背侧闭合负调控因子。Acal代表了JNK调控的一个新层次。Acal基因座编码一种保守的、长的、非编码的核RNA。长链非编码RNA是一类丰富多样的基因调控因子。Acal突变是致死性的。Acal mRNA表达是动态的，并被加工成一系列50至120个碱基对的片段。我们表明Acal位于先驱蛋白Raw的下游，这有助于解释Raw部分功能，并与多梳蛋白发生遗传相互作用。Acal在反式作用中调节参与JNK信号通路和背侧闭合的两个基因的mRNA表达：激酶与AP1的连接蛋白（Cka）和前开口（aop）。Cka是一种保守的支架蛋白，可将JNK和Jun聚集在一起，而aop是一种转录因子。Cka和aop的调控异常可解释Acal突变体中的背侧闭合表型。
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