Figure 6. Trans-competition control of splicing.

(A) Trans-competition control of alternative splicing. When competitor pre-mRNA levels are low, demand for the limiting factor (LF) is low resulting in efficient inclusion of the weakly competitive cassette exon. When competitor pre-mRNA levels are high, competitor pre-mRNAs titrate increased amounts of the limiting factor, resulting in much less efficient inclusion of the weakly competitive cassette exon. (B) Left Panel: Michaelis-Menten scheme showing two substrates with different affinities (S₁ and S₂) competing for the same enzyme, E. Formation of products P₁ and P₂ is determined by the concentration of each substrate and the substrate’s Km when the enzyme is limiting. Right Panel: Splicing scheme of two substrates competing for a limiting splicing machinery (pink circle). In this example, both substrates are present at the same initial concentration, but the orange substrate outcompetes the blue substrate due to its higher affinity (k1 ≫ k2). Note that rates of ES formation will also change between pre-mRNAs of equal affinity when one is at higher concentration. See also Fig S2.