ABSTRACT
Adaptation to different levels of illumination is central to the function of the retina. Here, we demonstrate that levels of the miR-183/96/182 cluster, miR-204, and miR-211 are regulated by different light levels in the mouse retina. Concentrations of these microRNAs were downregulated during dark adaptation and upregulated in light-adapted retinas, with rapid decay and increased transcription being responsible for the respective changes. We identified the voltage-dependent glutamate transporter Slc1a1 as one of the miR-183/96/182 targets in photoreceptor cells. We found that microRNAs in retinal neurons decay much faster than microRNAs in nonneuronal cells. The high turnover is also characteristic of microRNAs in hippocampal and cortical neurons, and neurons differentiated from ES cells in vitro. Blocking activity reduced turnover of microRNAs in neuronal cells while stimulation with glutamate accelerated it. Our results demonstrate that microRNA metabolism in neurons is higher than in most other cells types and linked to neuronal activity.
Subject(s)
MicroRNAs/metabolism , Neurons/metabolism , Animals , Dark Adaptation , Down-Regulation , Embryonic Stem Cells , Excitatory Amino Acid Transporter 3/genetics , Excitatory Amino Acid Transporter 3/metabolism , Mice , Photoreceptor Cells, Vertebrate/metabolism , Retinal Neurons/metabolism , Up-RegulationABSTRACT
Several microRNAs (miRNAs), including liver-specific miR-122, have been implicated in the control of hepatitis C virus (HCV) RNA replication and its response to interferon (IFN) in human hepatoma cells. Our analysis of liver biopsies from subjects with chronic hepatitis C (CHC) undergoing IFN therapy revealed no correlation of miR-122 expression with viral load and markedly decreased pretreatment miR-122 levels in subjects who had no virological response during later IFN therapy; other investigated miRNAs showed only limited changes. These data have implications for the prospect of targeting miRNAs for CHC therapy.
