Nathanael B. Kegel

Very interesting work: "Pseudouridine selects RNAs for extracellular transport"
www.biorxiv.org/content/10.1...

(1/2) Excited to share our new paper in @rheumjnl.bsky.social.We show that soluble BDCA-2 is elevated in rheumatoid arthritis and boosts IFN-α responses via nucleic acid binding. #Rheumatology #Diagnostics @unimarburg.bsky.social
academic.oup.com/rheumatology...

DNASE1L3 surveils mitochondrial DNA on the surface of distinct mammalian cells The extracellular space is a critical environment for discriminating self versus non-self nucleic acids and initiating the appropriate immune responses through signaling cascades to relay information ...

We’re excited to report work led by postdoc Jennifer Porat in the lab, finding that DNA accumulates on the surface of living cells and that the secreted extracellular protein DNASE1L3 can modulate its levels on B and T cells. With a new twist for ATAC-seq as well www.biorxiv.org/content/10.1...

Position of flask on magnetic stirrers can drastically affect reproducibility of experiments Comprehensive examination reveals improper siting of reaction vessels can affect catalyst formation, alter nanoparticle formation and change yields

New research shows that simply changing how a reaction vessel is positioned on a magnetic stirrer can significantly change a reaction's speed and product quality, influencing the reproducibility of results. #ChemSky #ScienceSky #EduSky

#savealldogs #dogs #dogsrule

Extracellular exosomal RNAs are glyco-modified - Nature Cell Biology Sharma, Jiao and colleagues report glycosylation of small RNAs within exosomes and propose a glycosylation-dependent mechanism for RNA targeting into exosomes, which may influence intercellular commun...

🤔
www.nature.com/articles/s41...

An Expanded View of RNA Modification with Carbohydrate-Based Metabolic Probes The discovery of glycosylated RNA (glycoRNA) revealed an unexpected association between glycans and RNA. This discovery, facilitated by the metabolic carbohydrate reporter per-O-acetylated N-azidoacet...

A highly interesting read from Hazemi et al., investigating the incorporation of a panel of azido sugars into RNA preps. Includes investigations of the high apparent MW shift of glycoRNA, the testing of proteinase K protocols, and non-enzymatic glycoRNA labelling.

pubs.acs.org/doi/full/10....

PhD Timeline xkcd.com/3081

We initiated our studies shortly after the first Cell paper was published. Back then, we were among the first to work on glycoRNA in our field (immunology). Thus, at least in our field, there was not much controversy. I understand the situation was probably different among e.g. glycobiologists

However, as we found glycoproteins in our glycoRNA samples, we stopped the functional analyses and rather focused on identifying which and also why proteins are co-purified, thinking this might help others with interest in glycoRNA‘s function

Regarding the question why resources were dedicated, we are a lab that’s interested in nucleic acid sensing. We were asking if RNA glycosylation affects recognition by innate immune receptors.

RNA-Associated Glycoconjugates Highlight Potential Ambiguities in glycoRNA Analysis A recent ground-breaking study suggested that small RNA from mammalian cells can undergo N-glycan modifications (termed glycoRNA) 1. The discovery relied upon a metabolic glycan labeling strategy in c...

Here is an updated version of a preprint posted in 2024: It describes a non-RNA glycoconjugate persisted throughout RNA sample processing, with similar electrophoretic properties and enzymatic reactivity as glycoRNA. It confounds gel-/blot-based glycoRNA assays.
www.biorxiv.org/content/10.1...

75% of US scientists who answered Nature poll consider leaving More than 1,600 readers answered our poll; many said they were looking for jobs in Europe and Canada.

The massive changes in US research brought about by the new administration of President Donald Trump are causing many scientists in the country to rethink their lives and careers

https://go.nature.com/41OhAgK

Cell-Surface RNA Forms Ternary Complex with RNA-Binding Proteins and Heparan Sulfate to Recruit Immune Receptors Recent discoveries have shown the presence of RNA molecules on the cell surface, defying the traditional view that RNA only functions intracellularly. However, it is not well understood how cell-surfa...

Excited to share an update on heparan sulfate (HS)-associated cell-surface RNA (hepRNA):
www.biorxiv.org/content/10.1...

Synthesis and structure elucidation of the human tRNA nucleoside mannosyl-queuosine - Nature Communications Mannosyl-queuosine (manQ) is a non-canonical RNA nucleoside present in the anticodon loop of certain tRNAs. Here, the authors use a combination of total synthesis and mass spectrometry to contradict t...

The lab of Thomas Carell has also provided structural analysis & more, see e.g. here:

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

Future studies may leverage proteinase K digestion under denaturing conditions to separate glycoRNA from glycoproteins — paving the way for deeper structural and functional insights into glycoRNA. (9/9)

We hypothesize that glycosylation and RNA-binding properties contribute to protein protection during glycoRNA isolation and promote co-purification by enhancing hydrophilicity and shielding cleavage
sites. (8/9)

Remarkably, recombinant LAMP1 was extractable from the aqueous phase of TRIzol and bound to silica
columns in an RNA- and alcohol concentration-dependent manner, consistent with observations by Kim et al. (2024) (7/9)

Nearly all of these proteins are known to be glycosylated and/or possess RNA-binding properties. One particularly intriguing hit was LAMP1, which we used as a model to explore glycoprotein co-purification. (6/9)

In an inspiring collaboration with @hoeferlab.bsky.social and @nursedayilmaz.bsky.social, we identified ten proteins that consistently co-purify with small, but not large, RNA fractions extracted from human and murine cell lines using LC-MS. (5/9)

To further investigate the nature of these RNase-resistant glyco-molecules, we tested their sensitivity to proteinase K digestion under denaturing conditions. Strikingly, they were degraded, suggesting that some glycoproteins co-purify with RNA during glycoRNA isolation. (4/9)

N-glycosylated molecules act as a co-precipitant in RNA purification A recent ground-breaking study suggested that small RNA from mammalian cells can undergo N-glycan modifications (termed glycoRNA) [1][1]. The discovery relied upon a metabolic glycan labeling strategy...

This was also reported by Kim et al. (2024): www.biorxiv.org/content/10.1... (3/9)

Like many in the field, we were fascinated by the discovery that RNA can be glycosylated. A key feature of glycoRNA is its sensitivity to RNase treatment. However, we observed that glycoRNA preparations contain not only glycoRNA but also RNase-resistant glyco-molecules. (2/9)

Proteins are a source of glycans found in preparations of glycoRNA Recent discoveries show that RNA can be modified with sialylated glycans (termed glycoRNA), thus broadening our understanding of cellular glycosylation beyond traditional proteins and lipids. However,...

Excited to share our preprint about proteins that we found in preparations of glycoRNAs now available on bioRxiv! #glycotime (1/9)
www.biorxiv.org/content/10.1...

Proteins are a source of glycans found in preparations of glycoRNA https://www.biorxiv.org/content/10.1101/2025.03.17.643711v1