Upstream of N-Ras C-terminal cold shock domains mediate poly(A) specificity in a novel RNA recognition mode and bind poly(A) binding protein

RNA binding proteins (RBPs) often engage multiple RNA binding domains (RBDs) to increase target specificity and affinity. However, the complexity of target recognition of multiple RBDs remains largely unexplored. Here we use Upstream of N-Ras (Unr), a multidomain RBP, to demonstrate how multiple RBDs orchestrate target specificity. A crystal structure of the three C-terminal RNA binding cold-shock domains (CSD) of Unr bound to a poly(A) sequence exemplifies how recognition goes beyond the classical pi pi-stacking in CSDs. Further structural studies reveal several interaction surfaces between the N-terminal and C-terminal part of Unr with the poly(A)-binding protein (pAbp). All interactions are validated by mutational analyses and the high-resolution structures presented here will guide further studies to understand how both proteins act together in cellular processes.

Automated summary

RNA binding proteins (RBPs) use multiple RNA binding domains (RBDs) to increase target specificity and affinity. However, the complexity of target recognition by multiple RBDs is not well understood. This study demonstrates how multiple RBDs in the multidomain RBP Unr orchestrate target specificity. Structural analysis reveals the interaction surfaces between Unr and the poly(A)-binding protein (pAbp), providing insights into their cooperative role in cellular processes.