RT Journal Article
SR Electronic
T1 Altered levels of hsromega lncRNAs further enhance Ras signaling during ectopically activated Ras induced R7 differentiation in Drosophila
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 224543
DO 10.1101/224543
A1 Mukulika Ray
A1 Gunjan Singh
A1 Subhash C. Lakhotia
YR 2019
UL http://biorxiv.org/content/early/2019/04/13/224543.abstract
AB 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>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 hsrω levels were co-altered. RNA-sequencing revealed that down-and up-regulation of hsrω 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 hsrω 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 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.Highlights 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.