CaMK IV Controls Splicing

Science's STKE  24 Apr 2001:
Vol. 2001, Issue 79, pp. tw2
DOI: 10.1126/stke.2001.79.tw2

Many mRNAs are alternatively spliced to produce proteins with different functions or regulatory properties. Diversity in the BK (also known as Slo) family of potassium channels arises through alternative splicing, and inclusion of the STREX exon produces a channel with higher sensitivity to calcium. Xie and Black show that inclusion of the STREX exon is decreased when GH3 pituitary cells are depolarized. By using a splicing reporter construct and cotransfection of calcium-calmodulin kinase (CaMK) isoforms, CaMK IV was identified as the isoform able to repress inclusion of the STREX exon from transcripts produced from the reporter. Two sequences were found to be important for CaMK IV regulation of splicing: an exonic pyrimidine-rich repressor element (D56) and a sequence upstream of the 3′ splice site of the STREX exon called the CaMK IV-responsive RNA element (CaRRE). CaMK IV was also able to regulate the splicing of another Slo exon and two exons of the N-methyl-D-aspartate receptor. Thus, modification of splicing to produce different channels through activation of CaMK IV represents one mechanism of activity-dependent alterations in channel expression that can lead to synaptic plasticity.

J. Xie, D. L. Black, A CaMK IV responsive RNA element mediates depolarization-induced alternative splicing of ion channels. Nature 410, 936-939 (2001). [Online Journal]