Abstract
We examined roles of hsrω lncRNAs in Ras signaling by down- or up-regulating them in sevGAL4 driven activated RasV12 expressing Drosophila eye discs. Late pupal lethality and extra R7 photoreceptors in ommatidia caused by sev-GAL4>RasV12 expression were significantly enhanced following simultaneous down- or up-regulation of hsrω lncRNAs. Ras signaling increased cell autonomously as well as non-autonomously, as revealed by enhanced p-MAPK expression, reduced Yan levels, greater RafRBDFLAG associated Ras and more R7 rhabdomeres. The further enhanced elevated Ras signaling seems to be due to post-transcriptional modifications in activities of Ras and its down-stream signaling members because of the disrupted intra-cellular dynamicity of many omega speckle associated hnRNPs and other RNA-binding proteins following down- or up-regulation of hsrω lncRNAs in elevated active Ras background. Co-altered hsrω RNA levels also modulated expression of certain sn/sno/scaRNAs and some other RNA processing genes affected in sev-GAL4>RasV12 discs. Down-regulation of hsrω transcripts in such background elevated positive modulators of Ras signaling while hsrω up-regulation reduced negative-modulators, further enhancing Ras signaling in either condition. Cell autonomous and non-autonomous enhancement of hyperactive Ras by lncRNAs has implications for cell signaling during normal and high Ras activity, commonly associated with some cancers.
Summary Our findings highlight roles of hsrω lncRNAs in conditionally modulating the important Ras signaling pathway and provide evidence for cell non-autonomous Ras signaling in Drosophila eye discs.