Figure 6

Unexpected novel CaMKII splice-variants that lack part of hub domain exon h2. (a) CaMKIIβ exon v2 contains an additional splice acceptor, that appears to be utilized only when exon v1 is skipped, such as in the originally described βe variant; here, sequence analysis additionally showed a βe variant without the one amino acid insertion created by the additional splice acceptor. (b) Partial skipping of hub domain exon h2 generates the novel CaMKIIβ splice variant βH. This is enabled by an additional splice acceptor site within exon h2. (c) The CaMKIIβ exon h2 internal splice site has the consensus sequence for splice acceptor sites that is conserved among species. The same consensus site is found also in CaMKIIδ, but not α or γ. RNA Seq of the rat hippocampal CA1 region detected alternative h2 splicing only in the β isoform (with percentage of transcripts indicated), but in none of the other isoforms. (d) The novel CaMKIIβH is a minor splice variant in all mouse brain regions, as shown by RT-PCR with primers flanking exon h2 (with primers directed against exons v4 and h3). (e) CaMKIIβH is a minor splice also during mouse embryonal development (from embryonal day E10 to E18) and in mature mouse skeletal muscle and pancreas (two of the few non-brain tissues with any CaMKIIβ expression).