Long noncoding RNAs are emerging as key players in various fundamental biological processes. We highlight the varied molecular mechanisms by which lncRNAs modulate gene expression in diverse cellular contexts and their role in early mammalian development in this review. Furthermore, it is being increasingly recognized that altered expression of lncRNAs is specifically associated with tumorigenesis, tumor progression and metastasis. We discuss various lncRNAs implicated in different cancer types with a focus on their clinical applications as potential biomarkers and therapeutic targets in the pathology of diverse cancers.

This study reports the identification and characterization of a novel gene, Dic61B, required for male fertility in Drosophila. Complementation mapping of a novel male sterile mutation, ms21, isolated in our lab revealed it to be allelic to CG7051 at 61B1 cytogenetic region, since two piggyBac insertion alleles, CG7051c05439 and CG7051f07138 failed to complement. CG7051 putatively encodes a Dynein intermediate chain. All three mutants, ms21, CG7051c05439 and CG7051f07138, exhibited absolute recessive male sterility with abnormally coiled sperm axonemes causing faulty sperm individualization as revealed by Phalloidin staining in Don Juan-GFP background. Sequencing of PCR amplicons uncovered two point mutations in ms21 allele and confirmed the piggyBac insertions in CG7051c05439 and CG7051f07138 alleles to be in 5′UTR and 4th exon of CG7051 respectively, excision of which reverted the male sterility. In situ hybridization to polytene chromosomes demonstrated CG7051 to be a single copy gene. RT-PCR of testis RNA revealed defective splicing of the CG7051 transcripts in mutants. Interestingly, expression of cytoplasmic dynein intermediate chain, α, β, γ tubulins and α-spectrin was normal in mutants while ultra structural studies revealed defects in the assembly of sperm axonemes. Bioinformatics further highlighted the homology of CG7051 to axonemal dynein intermediate chain of various organisms, including DNAI1 of humans, mutations in which lead to male sterility due to immotile sperms. Based on these observations we conclude that CG7051 encodes a novel axonemal dynein intermediate chain essential for male fertility in Drosophila and rename it as Dic61B. This is the first axonemal Dic gene of Drosophila to be characterized at molecular level and shown to be required for spermatogenesis.

In the pathogenesis of Alzheimer's disease (AD), it is well established that the self-association of Aβ peptides into amyloid fibrils and/or plaque like aggregates causes neurotoxicity. As there is no cure for AD till date, identification of specific compounds that either inhibit the formation of Aβ-fibrils or help in the dissolution of already formed amyloid plaques makes an appealing therapeutic and preventive strategy in the development of drugs. In the present study, four synthetic flavonoid derivatives (1, 2, 3 and 4) were examined for docking studies with Amyloid beta (PDB Code: 1IYT) and Amyloid fibril (PDB Code: 2BEG). Of these, compound 1 and 4 were found to be potential inhibitors, as supported by computational molecular docking studies with adequate pharmacokinetic properties. Compound 1 was further tested in vivo in transgenic AD model of Drosophila. The disease causing human Aβ42 peptide was expressed in the compound eye by driving UAS-Aβ42 with ey-GAL4, which caused severe degeneration in eye tissues ranging from loss of bristles, ommatidial holes to severe ommatidial disruption as revealed by digital camera imaging and scanning electron microscopy. When the Aβ42 expressing larvae were grown in medium containing Compound 1, ~70 % rescue of the rough eye phenotype was observed at 75 and 100 μM concentrations. This is further corroborated by significant reduction in amyloid plaques in eye imaginal disks of compound 1 treated larvae as revealed by immuno-confocal imaging studies. Further, rescue of locomotor deficit and improved life span in compound 1 treated Aβ flies also confirm the neuroprotective activity of this compound. Thus, our results support the neuroprotective efficacy of compound 1 in preventing Aβ42-induced neurotoxicity in vivo and identify it as a future therapeutic agent against AD.

The hsrω 05241 allele of the noncoding hsrω gene of Drosophila melanogaster is not responsible for male sterility as reported earlier