Natural display of nuclear-encoded RNA on the cell surface and its impact on cell interaction

Summary

This discovery study asks whether nuclear-encoded RNA is stably displayed on the outside of cells and whether such molecules participate in cell interactions. The authors developed Surface-seq to selectively sequence membrane-associated extracellular RNAs, then validated two candidates by RNA fluorescence in situ hybridization. To resolve cell-type specificity in human peripheral-blood mononuclear cells, they combined extracellular antisense-oligonucleotide labeling with imaging flow cytometry, single-cell RNA sequencing, and maxRNA sequencing. Monocytes emerged as the predominant maxRNA-positive population, and the integrated analysis prioritized eleven surface RNA candidates for functional testing. Applying antisense oligonucleotides against exposed FNDC3B or CTSS transcripts reduced monocyte adhesion to vascular endothelial cells. The principal finding is therefore not only that nuclear transcripts can be detected on the extracellular face of a cell, but that at least two such signals influence a defined cell–cell interaction. This expands the recognized molecular composition of the cell surface beyond proteins, glycans, and lipids. Its significance is a new layer of potential biomarkers and intervention targets in cell communication. The abstract does not establish how the RNAs are anchored, transported, or regulated, nor whether the antisense effects operate through direct steric blockade or another mechanism.