Interaction of the non-protein-coding developmental and stress-induciblehsrω gene withRas genes ofDrosophila melanogaster

Altered levels ofhsromegalncRNAs further enhance Ras signaling during ectopically activated Ras induced R7 differentiation inDrosophila

“…Although, some studies have implicated oncogenic Ras to influence expression of several long non coding transcripts (Jiang et al, 2017;Jinesh et al, 2018;Kotake et al, 2016;Rotblat et al, 2011;Zhang et al, 2017b), regulation of Ras signaling cascade by lncRNAs is not yet known. While an earlier study from our lab showed that a ras mutant allele enhanced hsrω-null phenotype (Ray and Lakhotia, 1998), the present study shows that alterations in levels of hsrω transcripts exaggerate phenotypes that follow the sev-GAL4 driven expression of activated Ras in developing eye discs of Drosophila larvae. The UAS-Ras V12 transgene (Karim et al, 1996) has been widely used for examining consequence of ectopic expression of ligand-independent activated Ras.…”

“…Besides their roles in developmental regulation (Katsushima et al, 2016;Kotake et al, 2016;Lakhotia, 2017b;Misawa et al, 2017;Zhang et al, 2017a), diverse lncRNAs have been reported to interact with components of the various signaling pathways in cancer, activating or repressing their strength and thus affecting outcomes like cell proliferation or apoptosis (Lakhotia, 2016;Liu et al, 2015;Wang et al, 2015). An earlier study (Ray and Lakhotia, 1998) from our laboratory showed that mutant alleles of ras (ras E62K and ras D38N ) dominantly enhanced the lethality due to nullisomic condition of the hsrω gene, which produces multiple lncRNAs (Lakhotia, 2011;Lakhotia, 2017a). The RAS/RAF/MAPK signaling pathway regulates many developmental pathways as it affects cell division, proliferation, growth as well as death, besides its major roles in many human cancers (Fernández-Medarde and Santos, 2011;Pylayeva-Gupta et al, 2011).…”

Activated Ras/JNK driven Dilp8 in imaginal discs adversely affects organismal homeostasis during early pupal stage in Drosophila, a new checkpoint for development

“…Earlier studies in our and other labs have shown that the hsrω lncRNA gene in Drosophila melanogaster regulates many cellular regulatory pathways through diverse mechanisms, of which the modulation of dynamics of heterogeneous nuclear RNA binding proteins (hnRNPs) and certain other RNA binding proteins seems to be a major component . We had earlier found a genetic interaction between Hsp83, Ras signaling pathways and the hsrω lncRNAs . Confirming these earlier studies, more recently we found that the ectopically induced high level of Ras signaling cascade was further enhanced when hsrω lncRNA levels were simultaneously downregulated in eye discs of Drosophila third instar larvae .…”

The Developmentally Active and Stress-Inducible Noncoding hsrω Gene Is a Novel Regulator of Apoptosis in Drosophila

“…Of the multiple noncoding transcripts produced by this locus, the nucleus limited hsrv-n transcript colocalizes with a variety of heterogeneous nuclear RNA-binding proteins (hnRNPs) to form fine nucleoplasmic omega speckles, which act as dynamic sinks to regulate the trafficking of hnRNPs and other related RNA-binding proteins (Lakhotia et al 1999;Prasanth et al 2000;Jolly and Lakhotia 2006). The hsrv transcripts play a crucial role in normal development and differentiation in the fly, since nullisomy for this gene leads to a high degree of embryonic lethality (Ray and Lakhotia 1998). All Drosophila species show a functional homolog of this gene (Lakhotia and Singh 1982; Mutt and S. C. Lakhotia, unpublished data).…”