The current paradigm of RNA-binding proteins is that they contain regions, or domains, that fold tightly into an ordered interaction platform that mediate RNA binding. In this review, we describe how this paradigm has been challenged by studies showing that other, hitherto neglected regions in RNA-binding proteins, which in spite of being intrinsically disordered, can play key functional roles in protein-RNA interactions. Proteins harbouring such disordered regions are involved in virtually every step of RNA regulation and, in some instances, have been implicated in disease. Based on exciting recent discoveries that indicate their unexpectedly pervasive role in RNA binding, we propose that the systematic study of disordered regions within RNA-binding proteins will shed light on poorly understood aspects of RNA biology and their implications in health and disease.
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