Cooperativity in RNA–protein interactions: the complex is more than the sum of its partners

• Neuropathologies are often linked to mutations in RNA-binding proteins (RBPs).
• RBPs recognise their targets in combination with other RBPs.
• Depending on the combination, the same RBP can attract different effector proteins.
• The study of RBP interaction networks is necessary to understand causes of neurological disorders.

Mutations in RNA-binding proteins (RBPs) are often linked to specific neurological disorders, suggesting that each of these RBPs regulates a particular neuronal function. Instead, they recognise many mRNAs and often participate in various post-transcriptional processes. To gain specificity, RBPs bind to RNA in collaboration with other RBPs. This model also explains how an RBP can play diverse roles: many RBPs do not contain an effector domain, which joins the RNA–protein complex as an additional unit. Different complexes, even if anchored on the same RBP, recruit diverse effectors. Therefore, the combination of RBPs determines the fate of an mRNA. We argue that new experimental and bioinformatic paradigms are needed to elucidate the combination of RBPs acting on a given mRNA.