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Reposted by Vincent Graziano

Krutika Kuppalli, MD FIDSA @krutikakuppalli.bsky.social · Aug 29

Don’t trust the experts”? That’s not democracy, that’s recklessness.

On a plane, I want a pilot.
In a hospital, I want doctors and scientists who understand the evidence.

Expertise isn’t religion or authoritarianism — it’s training, accountability, and data.

Ignore it and we all pay the price.

Republicans Against Trumpism @rpsagainsttrump.bsky.social · Aug 29

RFK Jr: We need to stop trusting the experts... Trusting the experts is not a feature of science or democracy, it's a feature of religion and totalitarianism.

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Reposted by Vincent Graziano

Ivan Zanoni @lozanzi.bsky.social · Aug 21

#InterferonPower! Thrilled for our latest work @cp-cell.bsky.social! With @danielboehmer.bsky.social, we dug into tons of papers & created what we hope will be a go-to resource for immunologists & non-immunologist about type I, II, III (& IV😉) #interferons! Free👉 authors.elsevier.com/a/1leKGL7PXu...

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Carolyn Bertozzi @carolynbertozzi.bskyverified.social · Aug 19

Another piece of the #glycoRNA puzzle revealed by @raflynn5.bsky.social and @vijayrathinam.bsky.social!! RNAs with modified base acp3U activate TLR3/7, but not when acp3U is N-glycosylated. This is how cell surface/secreted glycoRNAs avoid stimulating autoimmunity.

www.nature.com/articles/s41...

RNA N-glycosylation enables immune evasion and homeostatic efferocytosis - Nature

N-glycans on glycoRNAs prevent innate immune sensing of endogenous small RNAs, and the natural mechanism they use demonstrates how glycoRNAs exist on the cell surface and in the endosomal network with...

www.nature.com

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Reposted by Vincent Graziano

SfG @sfglycobiology.bsky.social · Aug 13

4/5 The Glycobiology Significant Achievement Award:
Dr. Ryan Flynn @raflynn5.bsky.social, Harvard University, 👏👏🥂

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Vincent Graziano @vinnieviruses.bsky.social · Aug 7

Thanks Dr. Doench! Hope you’re doing well!

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Reposted by Vincent Graziano

Waggoner Lab @labwaggoner.bsky.social · Aug 6

@vijayrathinam.bsky.social @vinnieviruses.bsky.social ‪@raflynn5.bsky.social‬ discovers why RNA undergoes glycosylation: N-glycans on glycoRNAs hide self-RNA from endosomal TLRs promoting ‘silent’ clearance of dead cells @nature.com
www.nature.com/articles/s41...

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Karim Majzoub @karimaj.bsky.social · Aug 6

Incredible discovery ! The first known role for sugar coated RNAs : immune evasion ! @raflynn5.bsky.social does it angain with @vinnieviruses.bsky.social @vijayrathinam.bsky.social and colleagues !

Ryan Flynn @raflynn5.bsky.social · Aug 6

RNA N-glycosylation enables immune evasion and homeostatic efferocytosis by chemically caging acp3U. Excited to report this work lead by Vinnie @vinnieviruses.bsky.social and in collaboration with @vijayrathinam.bsky.social in @nature.com www.nature.com/articles/s41...

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Madison (Maddi) Strine @madison-strine.bsky.social · Aug 6

Check out this @nature.com paper from the brilliant scientist I get to call my husband!!!!

Vincent Graziano @vinnieviruses.bsky.social · Aug 6

Hi everybody! I am super excited to share the work done during my PhD published in @nature today! We describe a new mechanism of self- vs. non-self RNA discrimination by showing how N-glycans shield glycoRNAs from stimulating endosomal RNA sensors www.nature.com/articles/s41...

RNA N-glycosylation enables immune evasion and homeostatic efferocytosis - Nature

N-glycans on glycoRNAs prevent innate immune sensing of endogenous small RNAs, and the natural mechanism they use demonstrates how glycoRNAs exist on the cell surface and in the endosomal network with...

www.nature.com

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Reposted by Vincent Graziano

Ryan Flynn @raflynn5.bsky.social · Aug 6

RNA N-glycosylation enables immune evasion and homeostatic efferocytosis by chemically caging acp3U. Excited to report this work lead by Vinnie @vinnieviruses.bsky.social and in collaboration with @vijayrathinam.bsky.social in @nature.com www.nature.com/articles/s41...

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Reposted by Vincent Graziano

Vijay Rathinam @vijayrathinam.bsky.social · Aug 6

Big congrats to Vinnie Graziano @vinnieviruses.bsky.social who led the project and huge thanks to our great collaborators: Jennifer Porat, Thomas Carell, Franck Barrat, Beiyan Zhou, Sivapriya Kailasan Vanaja, Michael Wilson, and Penghua Wang!! #innate_immunity #interferon #celldeath

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Vincent Graziano @vinnieviruses.bsky.social · Aug 6

Together, these data reveal one of potentially many answers to the question “why are RNAs glycosylated?” to which we found that it is to prevent autoinduction of RNA-sensing pathways.

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Vincent Graziano @vinnieviruses.bsky.social · Aug 6

Lastly, we found both TLR3 and TLR7 are required for sensing acp3U containing RNAs.

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Vincent Graziano @vinnieviruses.bsky.social · Aug 6

We teamed up with the Carell lab who synthesized an 18-nt long native or acp3U-containing RNA and found acp3U-RNAs were more immunostimulatory than the unmodified RNAs.

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Vincent Graziano @vinnieviruses.bsky.social · Aug 6

To our surprise, cells deficient in acp3U were not able to stimulate macrophages in both our transfection and efferocytosis assays.

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Vincent Graziano @vinnieviruses.bsky.social · Aug 6

Recently, it was found that acp3U (a hypermodified uridine) is an attachment site for N-glycans to RNA. Genetic KOs of the enzyme DTWD2 prevents the synthesis of acp3U resulting in decreased glycoRNA signal.

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Vincent Graziano @vinnieviruses.bsky.social · Aug 6

Injecting WT mice with deglycosylated apoptotic cells was also capable of inducing a localized RNA-driven innate immune response.

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Vincent Graziano @vinnieviruses.bsky.social · Aug 6

We found that treatment of apoptotic cells with PNGase F elicited a potent IFN response when fed to macrophages.

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Vincent Graziano @vinnieviruses.bsky.social · Aug 6

With this in mind, we asked if N-glycans on RNAs promotes the immunologically silent clearance of apoptotic debris through the process of efferocytosis.

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Vincent Graziano @vinnieviruses.bsky.social · Aug 6

Because glycoRNAs are predominantly on the cell surface, we asked how they would behave during apoptosis. For instance, apoptotic cells are cleared constitutively from our system without inducing inflammatory responses through the process of efferocytosis.

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Vincent Graziano @vinnieviruses.bsky.social · Aug 6

Next, we checked to make sure PNGase F was not acting on the cells to induce an IFN response. We treated long RNA fractions (containing no glycoRNAs) with or without PNGase F and observed no production of IFNb, confirming this requires deglycosylation of small RNAs.

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Vincent Graziano @vinnieviruses.bsky.social · Aug 6

Here, we harvested small RNA fractions (enriched for glycoRNA) and treated small RNAs with the N-glycosidase PNGase F. We found that removal of the N-glycan renders these RNAs immunogenic upon transfection. Addition of RNases was able to abrogate this response.

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Vincent Graziano @vinnieviruses.bsky.social · Aug 6

This led Vijay, Ryan and I to wonder how these RNAs could exist in close proximity to highly sensitive endosomal RNA sensors without stimulating them.

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Vincent Graziano @vinnieviruses.bsky.social · Aug 6

In 2021, Ryan Flynn and @carolynbertozzi.bskyverified.social discovered the existence of glycoRNAs which are localized to the cell surface. Since endocytosis is a constitutive cellular function, it is common to find cell surface molecules within the endosomal compartment.

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Vincent Graziano @vinnieviruses.bsky.social · Aug 6

First, I would just like to thank @raflynn5.bsky.social and my mentor @vijayrathinam.bsky.social for their tremendous support in this project. Without these two, this paper would not have come to fruition.
Major findings below!

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