Editors' ChoiceNeurobiology

Enter the Intron

See allHide authors and affiliations

Sci. Signal.  19 Feb 2008:
Vol. 1, Issue 7, pp. ec60
DOI: 10.1126/stke.17ec60

Intron-containing, incompletely spliced mRNAs are normally thought to be retained in the nucleus or degraded if they make it into the cytoplasm, but Bell et al. report that an intron-containing mRNA has a role in regulating the distribution of a K+ channel in neurons and can thus influence the firing properties of the cell. The authors studied large-conductance Ca2+-sensitive K+ (BKCa) channels, which are activated in response to changes in membrane potential and concentrations of intracellular calcium and thus modulate the firing properties of hippocampal neurons. An mRNA encoding the BKCa channel alpha subunit that contained intron 16 (i16) made up about 10% of the cytoplasmic transcripts encoding the channel protein as detected by a matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) base extension method in culture rat hippocampal neurons. The authors also developed a quantum dot-based in situ hybridization protocol that allowed them to detect the i16-containing transcript in the somatodendritic cytoplasm in a gradient, with the concentration decreasing in inverse proportion to the distance from the cell soma. Specific depletion of i16-containing mRNA with siRNA changed the localization of BKCa channels, making them less likely to localize with filamentous actin in dendritic spines. Depletion of the i16-containing mRNA also increased excitability of the treated neurons. The authors propose that these effects likely derive from expression of the alternatively spliced mRNA and suggest that cytoplasmically located intron-containing mRNA may provide a previously unrecognized mechanism by which neuronal membrane excitability can be controlled.

T. J. Bell, K. Y. Miyashiro, J.-Y. Sul, R. McCullough, P. T. Buckley, J. Jochems, D. F. Meaney, P. Haydon, C. Cantor, T. D. Parsons, J. Eberwine, Cytoplasmic BKCa channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons. Proc. Natl. Acad. Sci. U.S.A. 105, 1901-1906 (2008). [Abstract] [Full Text]