Abstract
To examine role of hsrω nuclear lncRNAs in Ras signaling cascade, we down- or up-regulated these transcripts in eye discs of Drosophila expressing sev-GAL4 driven activated rasV12 transgene. The sev-GAL4 driven RasV12 transgene expression dependent late pupal lethality and extra R7 photoreceptors in ommatidia, were significantly enhanced when levels of hsrω lncRNA were down/up-regulated. This was associated with enhanced p-MAPK expression, reduced Yan levels, and greater association of RafRBDFLAG with Ras, indicating elevated Ras activation which was both cell autonomous and non-autonomous. RNAseq analysis revealed significant increase in expression of certain sno/sn/scaRNAs and some RNA processing genes in sev-GAL4>RasV12 which was further modulated when hsrωRNA levels were co-altered. Down-regulation of hsrωRNAs elevated positive modulators of Ras signaling while their up-regulation reduced expression of negative modulators of Ras signaling, and thus both conditions have similar outcome. Further enhancement of activity of hyperactive Ras following changes in hsrω lncRNA levels in cell autonomous as well as non-autonomous manner emphasizes roles of lncRNAs in cell signaling during development and disease conditions associated with hyperactive Ras pathway mutants.
Summary Our findings highlight roles of hsrω lncRNA in conditionally modulating the important Ras signaling pathway and provide evidence for cell non-autonomous Ras signaling in Drosophila eye discs.
Footnotes
ORCID ID: Mukulika Ray: 0000-0002-9064-818X
S. C. Lakhotia: 0000-0003-1842-8411