Biology subjects

Lakhotia, S. C.

Publications and source records attributed to Lakhotia, S. C..

2 recordsLinked to original sources

bioRxiv2018

Over-expression of Hsp83 in grossly depleted hsrω lncRNA background causes synthetic lethality and l(2)gl phenocopy in Drosophila

We examined interactions between Hsp83 and hsr{omega} lncRNAs in hsr{omega}66 Hsp90GFP homozygotes, which almost completely lack hsr{omega} lncRNAs but over-express Hsp83. All +/+; hsr{omega}66 Hsp90GFP progeny died before third instar. Rare Sp/CyO; hsr{omega}66 Hsp90GFP reached third instar stage but phenocopied l(2)gl mutants, dying after prolonged larval life, becoming progressively bulbous and transparent with enlarged brain. Additionally, ventral ganglia were elongated. However, hsr{omega}66 Hsp90GFP/TM6B heterozygotes, carrying +/+ or Sp/CyO second chromosomes, developed normally. Total RNA sequencing (+/+, +/+; hsr{omega}66/hsr{omega}66, Sp/CyO; hsr{omega}66/hsr{omega}66, +/+; Hsp90GFP/Hsp90GFP, and Sp/CyO; hsr{omega}66 Hsp90GFP/hsr{omega}66 Hsp90GFP late third instar larvae) revealed similar effects on many genes in hsr{omega}66 and Hsp90GFP homozygotes. Besides additive effect on many of them, numerous additional genes were affected in Sp/CyO; hsr{omega}66 Hsp90GFP larvae, with l(2)gl and several genes regulating CNS being highly down-regulated in surviving Sp/CyO; hsr{omega}66 Hsp90GFP larvae, but not in hsr{omega}66 or Hsp90GFP single mutants. Hsp83 binds at these gene promoters. Several omega speckle associated hnRNPs too may bind with these genes and transcripts. Hsp83-hnRNP interactions are also known. Thus, elevated Hsp83 in altered hnRNP distribution and dynamics, following absence of hsr{omega} lncRNAs and omega speckles, background can severely perturb regulatory circuits with unexpected consequences, including down-regulation of tumor suppressor gene like l(2)gl.

developmental biology↗

bioRxiv2017

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

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.

cell biology↗