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In Drosophila melanogaster, miR-279 influences circadian rhythms by regulating the expression of the cytokine unpaired (upd). Flies with mutant alleles affecting miR-279 fail to maintain robust rest/activity rhythms when housed in free-running conditions (i.e. when they are maintained in the absence of any external cues). Given this phenotype, one might expect miR-279 to directly regulate clock genes within the core-clock neurons. However, this does not appear to be the case. Rather, miR-279 affects the output from core-clock neurons by post-transcriptionally regulating upd, a ligand for JAK/STAT signaling. Because miR-279 regulates upd, which is downstream of the circadian-activated Pigment-Dispersing Factor Receptor, miR-279 indirectly regulates JAK/STAT signaling. Similar to upd, modulating JAK/STAT signaling also affects circadian activity rhythms, suggesting that upd works through JAK/STAT signaling to affect this phenotype.

There is also evidence suggesting that the effect miR-279 on circadian rhythms requires a concurrent loss of function in a similar miRNA, miR-996. Flies with a double mutation for miR-279 and miR-996 have disrupted circadian rhythms, and restoring function in either of these microRNAs appears to restore circadian rhythms to a wild-type level. Given that miR-279 and miR-996 share a similar seed region (i.e. the a short span of nucleotides in the 5' end of the miRNA that determines mRNA specificity), they likely share similar mRNA targets. However, the role miR-996 in regulating upd expression and subsequently JAK/STAT activation has yet to be demonstrated in Drosophila.

Regulation of border cell fate via stat[edit]

Border cells in the ovary of Drosophila melanogaster are set of ~8 migratory cells that support the oocyte during oogenesis. The differentiation of these cells from the static follicular epithelium is set by a morphogen gradient, from the morphogen Unpaired (Upd). Like the aforementioned neuronal Upd, ovarian Upd acts as a ligand for JAK/STAT signaling. Elevated JAK/STAT signaling ensures that cells in the anterior follicular epithelium adopt a migratory border cell fate, whereas diminished JAK/STAT signaling does ensures the opposite. miR-279 fine-tunes JAK/STAT signaling in the ovary by negatively regulating stat (unlike the neurons, where it is reported to regulate upd)

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Comments

Overall, great content. Some minor issues - too many commas in the second sentence, I made some corrections to the article. Can you add any images to the article? Can you add more hyperlinks to other wikipedia pages? Can you group any of the sections under a subheading?-DJP

Article was clear and applied topics on nucleic acids to interesting questions of development in model organisms. Review on neuronal cell fate section needs reference(s). Knowledge seems beyond that which would be considered commonly known. All sections should have updated reference information to corroborate claims made in article. Overall, interesting focus of microRNA, and I look forward to reading this article in its final state. -JMR

The sections under Function are really interesting! I think you would benefit from describing mir-279 microRNA from a broader perspective. The intro could use some more detail or be fleshed out. For example, I am curious about what mir-279 is specifically? (Is it a gene? Do all organisms have it? Or just animals/higher organisms?) I have pretty limited biology knowledge, but from the introduction as it is I am having trouble appreciating why mir-279 is important (compared to other microRNAs? Why does mir-279 get its own Wikipedia page but not mir-996?) Also, there is some jargon that might not be super accessible (ectopic, pleiotropic, maxillary palp, some others) Also, I'm guessing the citations got lost when you copied this from the existing article, but don't forget to add those in :) -Kellie

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