Non-canonical subunit functions in multiprotein complexes: insights from the Mediator complex

The Mediator complex is a central regulator of RNA polymerase II transcription, integrating signals from transcription factors and coordinating pre-initiation complex assembly. Beyond this canonical role, numerous studies have implicated Mediator complex in diverse cellular processes, including RNA processing, DNA repair, and translational control. These observations raise a fundamental question: do such functions reflect an expansion of Mediator activity as a complex, or the emergence of specialized functions at the level of individual subunits? In this review, we examine the ability of Mediator subunits to function independently of their canonical context and discuss the mechanistic principles that enable subunit specialization within multiprotein assemblies.