A year and a half ago I wrote about a preprint showing that small RNA molecules are being glycosylated. Now this paper is published in Cell, with some additional data.
In particular, the work from Carolyn Bertozzi’s lab and led by (now new PI) Ryan Flynn, originally showed that the glyco-RNA associates with membranes. In the published work they show that it actually resides on the cell surface.
They use a variety of biochemical approaches to label the outer-surface glycoRNA, or stain it with an antibody that binds double-stranded RNA and visualize by FACS. Importantly, they show that sialic acid binding-immunoglobulin lectin-type (Siglec) receptor – proteins that are abundant on immune-cells surfaces and mediate a variety of immune responses – can also bind to the glycoRNA on the cell surface.
What is the role of glycoRNA on the cell surface? I made a few suggestions in my previous post. But i think now the most urgent experiment will be to use a known Siglec activation system and ask what happens if cells are pre-treated with RNase prior to interaction with Siglec-expressing immune cells.
Some very interesting questions:
- How is the glycoRNA targeted to the outer surface of the cell?
- Which proteins are involved?
- How is it protected from extracellular RNAses?
I’m looking forward to see the continuation of this fascinating new field of research.
Small RNAs are modified with N-glycans and displayed on the surface of living cells.
Ryan A. Flynn, Keyvon 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
Cell (2021) DOI: 10.1016/j.cell.2021.04.023
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