The RNA-Binding Properties of Annexins

Annexins are a family of calcium-dependent phospholipid-binding proteins involved in crucial cellular processes such as cell division, calcium signaling, vesicle trafficking, membrane repair, and apoptosis. In addition to these properties, Annexins have also been shown to bind RNA, although this function is not universally recognized. In the attempt to clarify this important issue, we employed an integrated combination of experimental and computational approaches. Using the catRAPID algorithm, we accurately predicted known RNA-binding partners of Annexins, supported by experimental validation. We then constructed a virtual library of potential mRNA partners for Annexin A2, identifying regions within its structure directly involved in RNA binding. Beyond RNA interaction, some Annexins, notably AnxA7 and AnxA11, exhibit strong phase separation tendencies driven by their N-termini. These biophysical properties likely play roles in RNA trafficking and localization particularly in neurons, where they may influence processes such as synaptic plasticity, learning, and memory. Our predictions contribute to a deeper understanding of the Annexin function, emphasizing their potential impact on RNA regulation and cellular compartmentalization through phase separation and propose a powerful computational tool for the prediction of RNA-binding properties.