Small RNAs are modified with N-glycans and displayed on the surface of living cells

Ryan A Flynn1, Kayvon Pedram2, Stacy A Malaker2, Pedro J Batista3, Benjamin A H Smith4, Alex G Johnson5, Benson M George6, Karim Majzoub7, Peter W Villalta8, Jan E Carette9, Carolyn R Bertozzi10

  1. Department of Chemistry, Stanford University, Stanford, CA, USA. Electronic address: ryan.flynn@childrens.harvard.edu.
  2. Department of Chemistry, Stanford University, Stanford, CA, USA.
  3. Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  4. Department of Chemical and Systems Biology and ChEM-H, Stanford University, Stanford, CA, USA.
  5. Department of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.
  6. Department of Cancer Biology, Stanford University, Stanford, CA, USA.
  7. Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA; IGMM, CNRS, University of Montpellier, Montpellier, France.
  8. Masonic Cancer Center and Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA.
  9. Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
  10. Department of Chemistry, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. Electronic address: bertozzi@stanford.edu.

Abstract

Glycans modify lipids and proteins to mediate inter- and intramolecular interactions across all domains of life. RNA is not thought to be a major target of glycosylation. Here, we challenge this view with evidence that mammals use RNA as a third scaffold for glycosylation. Using a battery of chemical and biochemical approaches, we found that conserved small noncoding RNAs bear sialylated glycans. These "glycoRNAs" were present in multiple cell types and mammalian species, in cultured cells, and in vivo. GlycoRNA assembly depends on canonical N-glycan biosynthetic machinery and results in structures enriched in sialic acid and fucose. Analysis of living cells revealed that the majority of glycoRNAs were present on the cell surface and can interact with anti-dsRNA antibodies and members of the Siglec receptor family. Collectively, these findings suggest the existence of a direct interface between RNA biology and glycobiology, and an expanded role for RNA in extracellular biology.

Presented By Ryan Flynn | ORCID iD

Biochemistry, Cell & Developmental BioNicholas Liao2021-06 (Jun)