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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.