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The production of two distinct functional microRNAs from opposite DNA strands by a single Hox locus in Drosophila is discussed.

Post-transcriptional gene regulation by the microRNA miR9a plays an important role in ensuring the precision of sense organ specification in Drosophila. The function of miR-9a is reported by generating a targeted knockout of a precursor hairpin in Drosophila melanogaster.

Evidence to show that the microRNA miR-278 plays a role in the control of energy homeostasis in Drosophila is presented. miR-278 acts by a different mechanism, at least partly through regulation of expanded transcript to control insulin sensitivity in adipose and peripheral tissues.

An enormous regulatory potential for microRNA (miRNAs) in gene expression programs, rivaling the complexity of the transcriptional control network is suggested. Understanding the role of miRNAs leads inevitably to the question of why certain gene expression events are targeted by miRNAs rather than by transcriptional repressors.

The relevance of 4E-BP function, an important regulator of overall translation levels in cells, for organismal development is discussed and evidence for an alternate view is presented. It is suggested that 4E-BP works as a metabolic break that is activated under conditions of environmental stress to control fat metabolism.

The Drosophila Sterile-20 kinase Slik promotes tissue growth during development by stimulating cell proliferation and by preventing apoptosis. It is observed that Slik acts via distinct pathways to coordinate cell proliferation with epithelial cell behavior during tissue growth.

LIM-homeodomain protein Apterous (AP) activity is essential to formation of the dorsal-ventral axis of the wing in Drosophila. The Ap activity levels are modulated by dLMO,a protein, which is encoded by the Beadex (Bx) gene. The dominant interference mechanism of dLMO action may be a suitable model for the way LMO oncogenes bring on leukemia and lymphoma when they are misexpressed in T cells.

The microRNA miR-14 modulates a positive autoregulatory loop by limiting the Drosophila Ecdysone receptor (EcR) gene.

A study focuses on the importance of phosphatidylinositol-3-kinase (PI3k)/AKT signaling in treating cancers, wherein enzymatic activity of AKT is shown to be dependent on phosphorylation of conserved sites by TOR (target of rapamycin) complex 2 (TORC2) in a Pl3K-dependent manner. Experiments show that TORC 2 acts as a rheostat to broaden the range of AKT signaling for tissue growth and metabolism.

Energy homeostasis depends on insulin signaling in metazoans. Insulin levels reflect the nutritional status of the animal to control levels of circulating sugar and regulate storage of resources in the form of glycogen and fat. Over the past several years, evidence has begun to accumulate that insulin production and secretion, as well as cellular responsiveness to insulin, are subject to regulation by microRNAs. Here we present evidence that miR- 14 acts in the insulin-producing neurosecretory cells in the adult Drosophila brain to control metabolism. miR-14 acts in these cells through its direct target, sugarbabe. sugarbabe encodes a predicted zinc finger protein that regulates insulin gene expression in the neurosecretory cells. Regulation of sugarbabe levels by nutrients and by miR-14 combines to allow the fly to manage resource mobilization in a nutritionally variable environment. [ABSTRACT FROM AUTHOR]

Homeostasis of the intestine is maintained by dynamic regulation of a pool of intestinal stem cells. The balance between stem cell self-renewal and differentiation is regulated by the Notch and insulin signaling pathways. Dependence on the insulin pathway places the stem cell pool under nutritional control, allowing gut homeostasis to adapt to environmental conditions. Here we present evidence that miR-305 is required for adaptive homeostasis of the gut. miR-305 regulates the Notch and insulin pathways in the intestinal stem cells. Notably, miR-305 expression in the stem cells is itself under nutritional control via the insulin pathway. This link places regulation of Notch pathway activity under nutritional control. These findings provide a mechanism through which the insulin pathway controls the balance between stem cell self-renewal and differentiation that is required for adaptive homeostasis in the gut in response to changing environmental conditions. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress is emerging as a potential contributor to the onset of type 2 diabetes by making cells insulin-resistant. However, our understanding of the mechanisms by which ER stress affects insulin response remains fragmentary. Here we present evidence that the ER stress pathway acts via a conserved signaling mechanism involving the protein kinase PERK to modulate cellular insulin responsiveness. Insulin signaling via AKT reduces activity of FOXO transcription factors. In some cells, PERK can promote insulin responsiveness. However, we found that PERK also acts oppositely via phosphorylation of FOXO to promote FOXO activity. Inhibition of PERK improves cellular insulin responsiveness at the level of FOXO activity. We suggest that the protein kinase PERK may be a promising pharmacological target for ameliorating insulin resistance. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are emerging as cooperating factors that promote the activity of oncogenes in tumor formation and disease progression. This poses the challenge of identifying the miRNA targets responsible for these interactions. In this study, we identify the growth regulatory miRNA bantam and its target, Socs36E, as cooperating factors in EGFR-driven tumorigenesis and metastasis in a Drosophila model of epithelial transformation. bantam promotes growth by limiting expression of Socs36E, which functions as a negative growth regulator. Socs36E has only a modest effect on growth on its own, but behaves as a tumor suppressor in combination with EGFR activation. The human ortholog of SOCS36E, SOCS5, behaves as a candidate tumor suppressor in cellular transformation in cooperation with EGFR/RAS pathway activation. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are 22-nucleotide RNAs that are processed from characteristic precursor hairpins and pair to sites in messages of protein-coding genes to direct post-transcriptional repression. Here, we report that the miRNA iab-4 locus in the Drosophila Hox cluster is transcribed convergently from both DNA strands, giving rise to two distinct functional miRNAs. Both sense and antisense miRNA products target neighboring Hox genes via highly conserved sites, leading to homeotic transformations when ectopically expressed. We also report sense/antisense miRNAs in mouse and find antisense transcripts close to many miRNAs in both flies and mammals, suggesting that additional sense/antisense pairs exist. [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) serve as post-transcriptional regulators of gene expression, by guiding effector complexes (miRNPs) to target RNAs. Although considerable progress has been made in computational methods to identify miRNA targets, only a relatively limited assessment of their ability to function in vivo has been reported. Here we describe an alternative approach to miRNA target identification based on a biochemical method for purifying miRNP complexes with associated miRNAs and bound mRNA targets. Microarray analysis revealed a high degree of enrichment for miRNA complementary sites in the 3'UTRs of the miRNP-associated mRNAs. mRNAs specifically associated with an individual miRNA were identified by comparing the miRNP-associated mRNAs from wild-type flies and mutant flies lacking miR-1, and their regulation by the miRNA was validated. This approach provides a means to identify functional miRNA targets based on their physical interaction in vivo.