Activity-dependent spatially localized miRNA maturation in neuronal dendrites.
MicroRNAs (miRNAs) regulate gene expression by binding to target messenger RNAs (mRNAs) and preventing their translation. In general, the number of potential mRNA targets in a cell is much greater than the miRNA copy number, complicating high-fidelity miRNA-target interactions. We developed an inducible fluorescent probe to explore whether the maturation of a miRNA could be regulated in space and time in neurons. A precursor miRNA (pre-miRNA) probe exhibited an activity-dependent increase in fluorescence, suggesting the stimulation of miRNA maturation. Single-synapse stimulation resulted in a local maturation of miRNA that was associated with a spatially restricted reduction in the protein synthesis of a target mRNA. Thus, the spatially and temporally regulated maturation of pre-miRNAs can be used to increase the precision and robustness of miRNA-mediated translational repression.
Max Planck Institute for Brain Research, Max-von-Laue Straße 4, 60438 Frankfurt, Germany.
Sivakumar
0000-0001-5471-6141
S
Sambandan
Max Planck Institute for Brain Research, Max-von-Laue Straße 4, 60438 Frankfurt, Germany.
Güney
0000-0002-3219-401X
G
Akbalik
Max Planck Institute for Brain Research, Max-von-Laue Straße 4, 60438 Frankfurt, Germany.
Lisa
L
Kochen
Institute for Organic Chemistry and Chemical Biology, Goethe University, 60438 Frankfurt, Germany.
Jennifer
J
Rinne
Institute for Organic Chemistry and Chemical Biology, Goethe University, 60438 Frankfurt, Germany.
Josefine
0000-0002-4165-0101
J
Kahlstatt
Max Planck Institute for Brain Research, Max-von-Laue Straße 4, 60438 Frankfurt, Germany.
Caspar
0000-0001-5873-1840
C
Glock
Max Planck Institute for Brain Research, Max-von-Laue Straße 4, 60438 Frankfurt, Germany.
Georgi
0000-0002-3340-9422
G
Tushev
Max Planck Institute for Brain Research, Max-von-Laue Straße 4, 60438 Frankfurt, Germany.
Beatriz
0000-0001-7505-1855
B
Alvarez-Castelao
Institute for Organic Chemistry and Chemical Biology, Goethe University, 60438 Frankfurt, Germany. heckel@uni-frankfurt.de erin.schuman@brain.mpg.de.|Cluster of Excellence "Macromolecular Complexes in Action," Goethe University, 60438 Frankfurt, Germany.
Alexander
0000-0003-3541-4548
A
Heckel
Max Planck Institute for Brain Research, Max-von-Laue Straße 4, 60438 Frankfurt, Germany. heckel@uni-frankfurt.de erin.schuman@brain.mpg.de.|Cluster of Excellence "Macromolecular Complexes in Action," Goethe University, 60438 Frankfurt, Germany.
Erin M
0000-0002-7053-1005
EM
Schuman
D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics*; D059367:RNA Cleavage; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
D005456:Fluorescent Dyes; C581717:MIRN181 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; D043244:Ribonuclease III