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bioRxiv · 10.1101/224543

Altered hsrω lncRNA levels in activated Ras background further enhance Ras activity in Drosophila eye and induces more R7 photoreceptors

Lakhotia, S. C.·Ray, M.
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Abstract

We exploited the high Ras activity induced differentiation of supernumerary R7 cells in Drosophila eyes to examine if hsr{omega} lncRNAs influence active Ras signaling. Surprisingly, either down- or up-regulation of hsr{omega} lncRNAs in sev-GAL4>RasV12 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 RasV12 bound RafRBDFLAG in cells not expressing the sev-GAL4 driver indicated non-cell autonomous spread of Ras signaling when hsr{omega} levels were co-altered. RNA-sequencing revealed that down-and up-regulation of hsr{omega} transcripts in sev-GAL4>RasV12 expressing eye discs elevated transcripts of positive or negative modulators, respectively, of Ras signaling so that either condition enhances it. Altered hsr{omega} transcript levels in sev-GAL4>RasV12 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 hsr{omega} lncRNAs appear to be responsible for the further elevated Ras signaling. Cell autonomous and non-autonomous enhancement of Ras signaling by lncRNAs like hsr{omega} has implications for cell signaling during high Ras activity commonly associated with some cancers.\n\nHighlightsOur findings highlight roles of hsr{omega} lncRNAs in conditionally modulating the important Ras signaling pathway and provide evidence for cell non-autonomous Ras signaling in Drosophila eye discs.

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Lakhotia, S. C., Ray, M.. 2017-11-24. Altered hsrω lncRNA levels in activated Ras background further enhance Ras activity in Drosophila eye and induces more R7 photoreceptors. https://doi.org/10.1101/224543

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