Characterizing light-regulated retinal microRNAs reveals rapid turnover as a common property of neuronal microRNAs.
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.
Krol
Jacek
J
Friedrich Miescher Institute for Biomedical Research, PO Box 2543, 4002 Basel, Switzerland.
Busskamp
Volker
V
Markiewicz
Ilona
I
Stadler
Michael B
MB
Ribi
Sebastian
S
Richter
Jens
J
Duebel
Jens
J
Bicker
Silvia
S
Fehling
Hans Jörg
HJ
Schübeler
Dirk
D
Oertner
Thomas G
TG
Schratt
Gerhard
G
Bibel
Miriam
M
Roska
Botond
B
Filipowicz
Witold
W
D000818:Animals; D003623:Dark Adaptation; D015536:Down-Regulation; D053595:Embryonic Stem Cells; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D055351:Retinal Neurons / Q000378:metabolism; D015854:Up-Regulation
D050580:Excitatory Amino Acid Transporter 3; D035683:MicroRNAs; C493399:Slc1a1 protein, mouse