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The Neuroprotective role of miR‐1017, a 3′ Tailed Mirtron
Author(s) -
Cruz Matthew,
Flynt Alex
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.757.11
Subject(s) - neurodegeneration , biology , neuroprotection , ectopic expression , microrna , neuroscience , microbiology and biotechnology , genetics , gene , disease , medicine
microRNAs (miRNAs) regulate the expression of most animal mRNAs. Due to the pervasive activity of these genes many roles have been identified in development and physiology, however many remain uncharacterized, especially non‐canonical family members. Here we identify a function of a 3′ tailed mirtron, miR‐1017. miR‐1017 is encoded within an intron of an Acetylcholine receptor, nAChRα2. Visualizing GFP driven by nAChRα2 transcriptional enhancer sequences showed the miR‐1017 host transcript is present in adult gustatory organs and the associated region of adult brains, specifically the suboesophageal ganglion. Consistent with a role in neurobiology, many miR‐1017 predicted targets have roles in neurons. Using mir‐1017 knock out (KO) flies, we found derepression of two targets: nAChRα5 and its host transcript nAChRα2. GFP driven by nAChRα2 in the mir‐1017 KO showed a broader expression pattern, suggesting a role in a negative feedback loop that modulates sensitivity of neurons to Acetylcholine (Ach). Numerous neurodegenerative diseases including Alzheimer's disease (AD) have shown that increased receptor activity causes reactive oxygen species to develop, which leads to neurodegeneration. Indeed, miR‐1017 KO presents reduced lifespan, poor climbing ability, and an increase in Cleaved Caspase staining in the CNS. miR‐1017 may function to limit Ach activity and protect from excitotoxic‐induced neurodegeneration. Interestingly, ectopic expression of miR‐1017 can rescue lifespan and neurological function in a fly AD model. This research demonstrates the importance of miRNA‐mediated gene regulation, even when enacted by non‐conventional species. Support or Funding Information NIH R15