Diagram of Ca⁺⁺ signal-regulation of alternative splicing. Shown in the middle is a cassette exon (e2) with two flanking introns (a and b) and constitutive exons (e1 and e3), with exonic and intronic cis-acting pre-mRNA elements as splicing enhancers (green, +) or silencers (red, −) and trans-acting splicing factors (ovals) indicated. Without signal stimulation (above), the pre-mRNA is spliced in two pathways (I and II) with a given ratio leading to the inclusion (I) or exclusion (II) of the alternative exon e2 and the respective lariats. With signal induction, like Ca⁺⁺ (below), one pathway (here for example, II, heavier arrows) over the other pathway (I) is favored in a particular cell to promote the production of one variant mRNA. Through this regulation, Ca⁺⁺ signals will change the relative ratio of the variant mRNA or protein isoforms of different properties. (?: mostly unknown intermediate steps).