title: 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.
authors.affiliation: Department of Microbiology, Immunology & Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095-1662, USA.
authors.forename: Jiuyong
authors.initials: J
authors.lastname: Xie
authors.forename: Calvin
authors.initials: C
authors.lastname: Jan
authors.forename: Peter
authors.initials: P
authors.lastname: Stoilov
authors.forename: Jennifer
authors.initials: J
authors.lastname: Park
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Black
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D016384:Consensus Sequence; D005091:Exons; D017930:Genes, Reporter; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D012313:RNA / Q000737:chemistry / Q000235:genetics*; D012322:RNA Precursors / Q000235:genetics; D051381:Rats; D020218:Response Elements / Q000502:physiology; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
chemical_list: D020746:Calcium Channels, L-Type; D012322:RNA Precursors; D012313:RNA; C517683:CAMK4 protein, human; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517685:Camk4 protein, mouse; C517686:Camk4 protein, rat