Most microRNAs (miRNAs) are processed by two ribonuclease III enzymes. The first cleavage is performed by Microprocessor that is composed of RNase III enzyme Drosha and DGCR8, and the second by another RNase III enzyme Dicer. There are many examples of miRNAs that are poor substrates for Drosha and Dicer, owing to their suboptimal structures. However, a number of these suboptimal miRNAs are known to be expressed at the same or higher level as their neighboring structurally-optimal miRNAs. Recent studies suggest that the clustered orientation of these suboptimal miRNAs is the explanation for this phenomenon. It has been observed that the biogenesis of these suboptimal miRNAs can be affected by the expression of their neighboring optimal miRNAs. This principle is expected to apply more broadly, as it has been shown that a large percentage of suboptimal miRNAs reside within operons.
Epigenetic gene regulation is essential for developmental processes. Eggless (Egg), the Drosophila orthologue of the mammalian histone methyltransferase, SETDB1, is known to be involved in the survival and differentiation of germline stem cells and piRNA cluster transcription during Drosophila oogenesis; however the detailed mechanisms remain to be determined. Here, using high-throughput RNA sequencing, we investigated target genes regulated by Egg in an unbiased manner. We show that Egg plays diverse roles in particular piRNA pathway gene expression, some long non-coding RNA expression, apoptosis-related gene regulation, and Decapentaplegic (Dpp) signaling during Drosophila oogenesis. Furthermore, using genetic and cell biological approaches, we demonstrate that ectopic upregulation of dpp caused by loss of Egg in the germarium can trigger apoptotic cell death through activation of two pro-apoptotic genes, reaper and head involution defective. We propose a model in which Egg regulates germ cell differentiation and apoptosis through canonical and noncanonical Dpp pathways in Drosophila oogenesis.
Peptides have been in the limelight, as therapeutic agents for cancer treatment through various applications due to their high target selectivity and exceptional ability to penetrate the cell membrane. Recent studies have revealed that synthesized peptides bind to hairpin structures of RNA that affect their activities such as changing the efficacy of microRNA maturation. MicroRNA-mediated p53 activation by the microRNA-29 (miR29) family is one of the most important regulatory pathways in cancer therapeutics. By targeting the suppressors of p53, a tumor suppressor protein, miR29 induces apoptosis of cancer cells through p53 stabilization. Here, we identify a novel synthesized amphiphilic peptide, LK-L1C/K6W/L8C, which enhances expression of miR29b and promotes p53 activity. In the presence of LK-L1C/K6W/L8C, pre-miR29b preferentially forms a complex with the Dicer protein through interaction of LK-L1C/K6W/L8C with the terminal loop region of pre-miR29b, leading to an increase in Dicer processing. Furthermore, LK-L1C/K6W/L8C stimulates apoptosis by improving p53 stability in miR29-inducible HeLa and MCF7 cells. Collectively, our study shows that a peptide can directly influence the miR29b-mediated p53 activation pathway in cancer cells. Therefore, our findings provide the basis for a new, potentially promising peptide-based drug for cancer therapy.
Honeybees are one of the most environmentally important insects, as their pollination of various plant species contributes to the balance among different ecosystems. It has been studied extensively for their unique attribute of forming a caste society. Unlike other insects, honeybees communicate socially by secreting pheromones or by exhibiting specific patterns of motion. In the honeybee industry, the Asian honeybees (Apis cerana) and the Western honeybees (Apis mellifera) are dominant species. However, molecular research on the transcriptomes of A. cerana has not been studied as extensively as those of A. mellifera. Therefore, in this study, caste-specific transcriptional differences were analyzed, which provides a comprehensive analysis of A. cerana. In our dataset, we analyzed gene expression profiles using organs from worker, drone, and queen bees. This gene-expression profile helped us obtain more detailed information related to organ-specific genes, immune response, detoxification mechanisms, venom-specific genes, and ovary development. From our result, we found 4096 transcripts representing different gene-expression pattern in each organ. Our results suggest that caste-specific transcripts of each organ were expressed differently even under natural conditions. These transcriptome-wide analyses provide new insights into A. cerana and that promote honeybee research and conservation.
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