Abstract
We examined roles of hsrω lncRNAs in Ras signaling by down- or up-regulating them in sev-GAL4 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>RasV12discs. 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 conditions. 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.
Footnotes
This is a revised version of an earlier preprint: Altered hsrω lncRNA levels in activated Ras background further enhance Ras activity in Drosophila eye and induces more R7 photoreceptors. bioRxiv, DOI: 10.1101/224543. Several figures have been revised and RNA-seq data for different genotypes have been added. Tables and figures in supplementary material have also been modified. Author order that was wrongly provided in the previous version is corrected
