Cellular and Molecular Life Sciences

, Volume 69, Issue 23, pp 4017–4027

MicroRNA-338 regulates the axonal expression of multiple nuclear-encoded mitochondrial mRNAs encoding subunits of the oxidative phosphorylation machinery

  • Armaz Aschrafi
  • Amar N. Kar
  • Orlangie Natera-Naranjo
  • Margaret A. MacGibeny
  • Anthony E. Gioio
  • Barry B. Kaplan
Research Article

DOI: 10.1007/s00018-012-1064-8

Cite this article as:
Aschrafi, A., Kar, A.N., Natera-Naranjo, O. et al. Cell. Mol. Life Sci. (2012) 69: 4017. doi:10.1007/s00018-012-1064-8

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.

Keywords

Axonal protein synthesis ATP synthesis Reactive oxygen species Neurite outgrowth Sympathetic neurons 

Abbreviations

H2DCFDA

5-(and-6)-Carboxy-2′, 7′-dichlorodihydrofluorescein diacetate

NDGA

Nordihydraguaiaretic acid

COX

Cytochorome oxidase

qRT-PCR

Quantitative real-time reverse transcriptase polymerase chain reaction

miRNA

MicroRNA

Copyright information

© Springer Basel AG (outside the USA) 2012

Authors and Affiliations

  • Armaz Aschrafi
    • 1
  • Amar N. Kar
    • 1
  • Orlangie Natera-Naranjo
    • 1
  • Margaret A. MacGibeny
    • 1
  • Anthony E. Gioio
    • 1
  • Barry B. Kaplan
    • 1
  1. 1.Laboratory of Molecular Biology, National Institute of Mental HealthNational Institutes of HealthBethesdaUSA