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

Ryan A Flynn; Kayvon Pedram; Stacy A Malaker; Pedro J Batista; Benjamin A H Smith; Alex G Johnson; Benson M George; Karim Majzoub; Peter W Villalta; Jan E Carette; Carolyn R Bertozzi

doi:10.1016/j.cell.2021.04.023

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

Cell. 2021 Jun 10;184(12):3109-3124.e22. doi: 10.1016/j.cell.2021.04.023. Epub 2021 May 17.

Authors

Affiliations

¹ Department of Chemistry, Stanford University, Stanford, CA, USA. Electronic address: [email protected].
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: [email protected].

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.

Keywords: RNA biology; glycoRNA; glycobiology; siglec; small RNAs.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Antibodies / metabolism
Base Sequence
Biosynthetic Pathways
Cell Line
Cell Membrane / metabolism*
Cell Survival
Humans
Mass Spectrometry
N-Acetylneuraminic Acid / metabolism
Polyadenylation
Polysaccharides / chemistry
Polysaccharides / metabolism*
RNA / chemistry
RNA / genetics
RNA / metabolism*
RNA, Untranslated / metabolism
Sialic Acid Binding Immunoglobulin-like Lectins / metabolism
Staining and Labeling

Substances

Antibodies
Polysaccharides
RNA, Untranslated
Sialic Acid Binding Immunoglobulin-like Lectins
RNA
N-Acetylneuraminic Acid

Abstract

Publication types

MeSH terms

Substances

Grants and funding