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

被引:342
作者
Flynn, Ryan A. [1 ,11 ,12 ]
Pedram, Kayvon [1 ]
Malaker, Stacy A. [1 ]
Batista, Pedro J. [2 ]
Smith, Benjamin A. H. [3 ]
Johnson, Alex G. [4 ]
George, Benson M. [5 ]
Majzoub, Karim [6 ,7 ]
Villalta, Peter W. [8 ,9 ]
Carette, Jan E. [6 ]
Bertozzi, Carolyn R. [1 ,10 ]
机构
[1] Stanford Univ, Dept Chem, Stanford, CA 94305 USA
[2] NCI, Lab Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[3] Stanford Univ, Dept Chem & Syst Biol & ChEM H, Stanford, CA USA
[4] Stanford Univ, Dept Chem & Syst Biol, Stanford, CA USA
[5] Stanford Univ, Dept Canc Biol, Stanford, CA USA
[6] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA
[7] Univ Montpellier, CNRS, IGMM, Montpellier, France
[8] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA
[9] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA
[10] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA
[11] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA
[12] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
基金
美国国家科学基金会;
关键词
SYSTEMIC-LUPUS-ERYTHEMATOSUS; SIALIC-ACID; Y RNAS; GLYCOSYLATION; EXPRESSION; ANTIBODIES; SIGLECS; BINDING; DSRNA; AUTOANTIBODIES;
D O I
10.1016/j.cell.2021.04.023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:3109 / +
页数:38
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