A consensus CaMK IV-responsive RNA sequence mediates regulation of alternative exons in neurons
Abstract
Neurons make extensive use of alternative pre-mRNA splicing to regulate gene expression and diversify physiological responses. We showed previously in a pituitary cell line that the Ca++/calmodulin-dependent protein kinase CaMK IV specifically repressed splicing of the BK channel STREX exon. This repression is dependent on a CaMK IV-responsive RNA element (CaRRE) within the STREX 3′ splice site. Here, we report that similar Ca++ regulation of splicing, mediated by L-type calcium channels and CaM kinase IV, occurs in cultured neurons and in the brain. We identify a critical CaRRE motif (CACATNRTTAT) that is essential for conferring CaMK IV repression on an otherwise constitutive exon. Additional Ca++-regulated exons that carry this consensus sequence are also identified in the human genome. Thus, the Ca++/CaMK IV pathway in neurons controls the alternative splicing of a group of exons through this short CaRRE consensus sequence. The functions of some of these exons imply that splicing control through the CaMK IV pathway will alter neuronal activity.
Keywords
Footnotes
-
↵1 Present address: Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, MB R3E 3J7, Canada
-
Article and publication are at http://www.rnajournal.org/cgi/doi/10.1261/rna.2171205.
-
- Accepted September 13, 2005.
- Received July 22, 2005.
- Copyright 2005 by RNA Society