The roles of alternative splicing in regulating the function of intrinsically disordered regions

Alternative splicing (AS) generates extensive transcriptomic complexity. However, how this myriad of detected AS events contribute to biological functionality is not well understood. In this talk, I will describe how exons regulated by alternative splicing show a strong tendency to modulate low affinity and transient short linear motif (SLiM)-mediated protein-protein interactions. I will illustrate this with an example of a mammalian-specific set of AS events. These events regulate the inclusion of repetitive GY-SLiMs within nearly all members of the heterogeneous nuclear ribonucleoprotein (hnRNP) A and D families of RNA binding proteins. The differential inclusion of these exons impacts the formation of hnRNP-driven higher-order protein assemblies required for the regulation of target AS events.

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