csRNA and heparan sulfate : cell surface ribonucleoproteins regulate HS-mediated signaling

In a recent study published in Nature , Peiyuan Chai et al. 1 uncovered a new layer of regulation of cell surface ribonucleoproteins (csRNPs) in heparan sulfate (HS)-mediated VEGF-A signal transduction (Fig. 1 ). The discoveries not only provide a new understanding of csRNPs, including newly identified glycoRNA in important biological processes, but also open a distinct avenue to explore the detailed mechanisms of how HS precisely regulates various cell signaling pathways. Fig. 1 The alternative text for this image may have been generated using AI. Full size image HS acts as a scaffold platform to regulate csRNAs' functions on the cell surface. a HS structure and domain organization. The modifications of its component sugars during biosynthesis (GlcNAc and GlcA or IdoA) result in the formation of distinct domains (such as VEGF 165 binding domains, rich in sulfation), which are responsible for interacting with different factors. 6-O -sulfated HS facilitates the cluster formation of HS, csRNAs, and csRBPs. 1 b HS serves as a scaffold to form a complex with csRNAs (including GlycoRNA) and csRBPs (such as cs-DDX21 and cs-hnRNP-U). csRNAs complete the binding of HS to VEGF 165 , thereby regulating HS-mediated VEGF 165 signal transduction. 1 In addition to remodeling HS-mediated biological functions, the csRNAs attached to the HS scaffold can interact with other factors and influence cell signal transduction or other biological processes. As demonstrated in another recent research, csRNA is capable of recruiting the immune receptor killer cell immunoglobulin-like receptor 2DL5 (KIR2DL5). 4 b of the figure was created in BioRender. Ling, J. (2026) https://biorender.com/pzsvz0z