Galectin-1-RNA interaction map reveals potential regulatory roles in angiogenesis

Hyperactive angiogenesis contributes to the immunosuppressive microenvironment important for immunotherapy. Galectin-1, encoded by LGALS1, can trigger the vascular signaling programs and mediate the anti-angiogenic treatment response. However, the mechanism through which galectin-1 regulates angiogenesis is poorly understood. It has been suggested that galectin-1 may associate with mRNAs in cells. This study applied the iRIP-seq methodology to study the potential role of galectin-1 as an RNA-binding protein. We found that galectin-1 interacts with a large number of mRNAs, with a preference for binding near stop codons and a preference for UGCA/UGGA and GAGCAG as binding motifs. Galectin-1 binds to the mRNAs of angiogenesis-associated genes including VEGFA, EGR1, and LAMA5, suggesting that galectin-1 may regulate angiogenesis via its mRNA-binding activity. We further show that shLGALS1 inhibits capillary tube formation in an in vitro angiogenesis assay and alters the expression levels of several galectin-1-bound angiogenesis-associated mRNAs. These results uncover a previously unrecognized mRNA-binding activity of galectin-1.