Activity-dependent spatially localized miRNA maturation in neuronal dendrites

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Science  10 Feb 2017:
Vol. 355, Issue 6325, pp. 634-637
DOI: 10.1126/science.aaf8995

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Intraneuronal control of protein expression

In cells and tissues, mRNA copy numbers far exceed the number of micro RNAs (miRNAs). How then can a miRNA effectively regulate translation of a particular target mRNA? Sambandan et al. used high-resolution in situ hybridization to detect precursor miRNA in rat neuronal dendrites. They introduced a fluorescent miRNA maturation reporter into hippocampal neurons and detected activity-dependent maturation of the probe in both the soma and dendrites. This local maturation of the miRNA was indeed associated with a local reduction in protein synthesis. Thus, localized miRNA maturation can modulate target gene expression with local and temporal precision.

Science, this issue p. 634


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.

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