title: MicroRNA-338 regulates the axonal expression of multiple nuclear-encoded mitochondrial mRNAs encoding subunits of the oxidative phosphorylation machinery.
abstract: MicroRNAs (miRNAs) constitute a novel class of small, non-coding RNAs that act as post-transcriptional regulators of gene expression. Remarkably, it has been shown that these small molecules can coordinately regulate multiple genes coding for proteins with related cellular functions. Previously, we reported that brain-specific miR-338 modulates the axonal expression of cytochrome c oxidase IV (COXIV), a nuclear-encoded mitochondrial protein that plays a key role in oxidative phosphorylation and axonal function. Here, we report that ATP synthase (ATP5G1), like COXIV mRNA, contains a putative miR-338 binding site, and that modulation of miR-338 levels in the axon results in alterations in both COXIV and ATP5G1 expression. Importantly, miR-338 modulation of local COXIV and ATP5G1 expression has a marked effect on axonal ROS levels, as well as axonal growth. These findings point to a mechanism by which miR-338 modulates local energy metabolism through the coordinate regulation of the expression of multiple nuclear-encoded mitochondrial mRNAs in the axon.
authors: Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892-1381, USA.
authors: Armaz
authors: A
authors: Aschrafi
authors: Amar N
authors: AN
authors: Kar
authors: Orlangie
authors: O
authors: Natera-Naranjo
authors: Margaret A
authors: MA
authors: MacGibeny
authors: Anthony E
authors: AE
authors: Gioio
authors: Barry B
authors: BB
authors: Kaplan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism*; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D009637:Masoprocol / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010117:Oxypurinol / Q000494:pharmacology; D012313:RNA / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D000077278:RNA, Mitochondrial; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D017783:Superior Cervical Ganglion / Q000166:cytology
chemical_list: D020413:3' Untranslated Regions; D004791:Enzyme Inhibitors; C573089:MIRN338 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; D000077278:RNA, Mitochondrial; D017382:Reactive Oxygen Species; D012313:RNA; D009637:Masoprocol; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; C573472:ATP synthase subunit 9, rat; D025261:Mitochondrial Proton-Translocating ATPases; D010117:Oxypurinol