We exploited the high Ras activity induced differentiation of supernumerary R7 cells in Drosophila eyes to examine if hsrω lncRNAs influence active Ras signaling. Surprisingly, either down- or up-regulation of hsrω lncRNAs in sev-GAL4>Ras^V12 expressing eye discs resulted in complete pupal lethality and substantially greater increase in R7 photoreceptor number at the expense of cone cells. Enhanced nuclear p-MAPK and presence of sev-GAL4 driven Ras^V12 bound RafRBDFLAG in cells not expressing the sev-GAL4 driver indicated non-cell autonomous spread of Ras signaling when hsrω levels were co-altered. RNA-sequencing revealed that down-and up-regulation of hsrω transcripts in sev-GAL4>Ras^V12 expressing eye discs elevated transcripts of positive or negative modulators, respectively, of Ras signaling so that either condition enhances it. Altered hsrω transcript levels in sev-GAL4>Ras^V12 expressing discs also affected sn/sno/sca RNAs and some other RNA processing transcript levels. Post-transcriptional changes due to the disrupted intra-cellular dynamicity of omega speckle associated hnRNPs and other RNA-binding proteins that follow down- or up-regulation of hsrω lncRNAs appear to be responsible for the further elevated Ras signaling. Cell autonomous and non-autonomous enhancement of Ras signaling by lncRNAs like hsrω has implications for cell signaling during high Ras activity commonly associated with some cancers.

我们利用高Ras活性诱导果蝇眼中多余R7细胞的分化，以检查hsrωlncRNA是否影响活性Ras信号传导。出人意料的是，无论是降频或上调hsrω在lncRNAs SEV-GAL4>的Ras ^V12表达眼光盘导致完全蛹杀伤力和在锥体细胞的费用在R7感光体数目显着更大的增加。不表达sev-GAL4驱动程序的细胞中增强的核p-MAPK和sev-GAL4驱动的Ras ^V12结合的RafRBDFLAG的存在表明hsrω时Ras信号的非细胞自主传播级别进行了共同更改。RNA测序显示，表达sev-GAL4> Ras ^V12的眼盘中hsrω转录物的上下调节分别提高了Ras信号的正向或负向调节子的转录本，因此任何一种情况都可以增强它。sev-GAL4 > Ras ^V12表达盘中hsrω转录水平的改变也影响了sn / sno / sca RNA和其他一些RNA处理转录水平。转录后的变化是由于ω散斑相关的hnRNPs和其他RNA结合蛋白在hsrω的下调或上调后细胞内动力的破坏所致lncRNA似乎是Ras信号进一步升高的原因。像hsrω之类的lncRNAs可以自主地和非自主地增强Ras信号传导，这通常与某些癌症相关的高Ras活性对细胞信号传导有影响。