Heterotypic RNA–protein (RNP) interactions regulate gene expression, yet the foundational principles governing functional RNP assembly remain largely unknown across most of the transcriptome. This knowledge gap persists in part because heterotypic interactions are highly idiosyncratic, making it difficult to define generalizable rules of engagement. To address this challenge, a new conceptual framework is needed to better understand how heterogeneity contributes to RNA-mediated gene expression. We propose that mutual allostery provides such a framework, both for rationalizing the biological mechanisms underlying gene regulation and for identifying new strategies to therapeutically target RNA. Allostery describes a phenomenon in which ligand binding at one site induces conformational changes at a distant interaction surface. In heterotypic RNPs, mutual allostery can impose more precise and stringent control over RNA biology, as the respective complexes display unique physicochemical properties. In my presentation, I will discuss case studies that provide evidence supporting mutual allostery as a potentially generalizable framework for interpreting the contributions of heterotypic interactions to RNA biology.
Blanton S. Tolbert (2026) studied this question.