Happy to share my PhD work on the regulatory mechanism of E3 ligase RNF213! RNF213 is not a monomer, but a dimer that switches between inhibited and activated states in an ATP-dependent manner. We tracked the activation mechanism and showed how disease mutations can destabilize the inhibited state.
October 12, 2026 at 9:34 AM
Happy to share my PhD work on the regulatory mechanism of E3 ligase RNF213! RNF213 is not a monomer, but a dimer that switches between inhibited and activated states in an ATP-dependent manner. We tracked the activation mechanism and showed how disease mutations can destabilize the inhibited state.
Before its role in infection, RNF213 was identified as a major susceptibility factor for Moyamoya disease, with its mechanism unknown. We found that disease mutations cluster near the dimer interface, so we asked, can these mutations disrupt RNF213 regulation?
October 12, 2026 at 9:34 AM
Before its role in infection, RNF213 was identified as a major susceptibility factor for Moyamoya disease, with its mechanism unknown. We found that disease mutations cluster near the dimer interface, so we asked, can these mutations disrupt RNF213 regulation?
Using cryo-EM, we showed that RNF213 forms a zinc-dependent 1.2 MDa dimer, occluding the E2 binding site and catalytic RZ domain to keep the E3 ligase inactive.
October 12, 2026 at 9:34 AM
Using cryo-EM, we showed that RNF213 forms a zinc-dependent 1.2 MDa dimer, occluding the E2 binding site and catalytic RZ domain to keep the E3 ligase inactive.
We found that some of these mutations rearrange RNF213 to prevent dimer-mediated inhibition. Cryo-EM, biochemical assays and cellular investigation revealed that some mutants can even achieve the active conformation in the absence of ATP, resulting in increased inflammatory signaling.
October 12, 2026 at 9:34 AM
We found that some of these mutations rearrange RNF213 to prevent dimer-mediated inhibition. Cryo-EM, biochemical assays and cellular investigation revealed that some mutants can even achieve the active conformation in the absence of ATP, resulting in increased inflammatory signaling.
Cells carefully monitor DNA and proteins, but how they detect and remove damaged glycogen is less clear. A study @nature shows that the E3 ligase RNF213 tags abnormal glycogen with ubiquitin, for disposal by autophagy, preventing the buildup of harmful polyglucosan in the brain.
shorturl.at/KnRDE
shorturl.at/KnRDE
www.nature.com
October 7, 2026 at 9:55 AM
Cells carefully monitor DNA and proteins, but how they detect and remove damaged glycogen is less clear. A study @nature shows that the E3 ligase RNF213 tags abnormal glycogen with ubiquitin, for disposal by autophagy, preventing the buildup of harmful polyglucosan in the brain.
shorturl.at/KnRDE
shorturl.at/KnRDE
Samuel J Belfer, Rohan Vij, Lauren A Beslow, Craig Press, Dhyanam P Shukla, Laura DiDomenico, Arastoo Vossough, Laura Caligiuri, Allison Hyland, Shih-Shen L Chen, and Adam J Kundishora
Early Severe Moyamoya Disease Due to a Monoallelic <em>RNF213</em> Variant in Monozygotic Twins
Moyamoya disease (MMD) is an arteriopathy causing pediatric ischemic stroke and is characterized by progressive stenosis of the intracranial internal carotid arteries. Although genetic risk factors have been identified, the pathogenesis of MMD remains incompletely understood, and significant gaps persist in linking genetic variation to disease mechanisms and outcomes. We describe ex-30 week monozygotic twins presenting with recurrent ischemic events beginning in infancy found to have bilateral...
www.neurology.org
October 7, 2026 at 4:00 PM
Samuel J Belfer, Rohan Vij, Lauren A Beslow, Craig Press, Dhyanam P Shukla, Laura DiDomenico, Arastoo Vossough, Laura Caligiuri, Allison Hyland, Shih-Shen L Chen, and Adam J Kundishora
RNF213 M1-ubiquitinates damaged mitochondria to activate pro-inflammatory NF-κB signaling https://www.biorxiv.org/content/10.64898/2026.09.21.752888v1
September 23, 2026 at 1:30 AM
RNF213 M1-ubiquitinates damaged mitochondria to activate pro-inflammatory NF-κB signaling https://www.biorxiv.org/content/10.64898/2026.09.21.752888v1
RNF213 M1-ubiquitinates damaged mitochondria to activate pro-inflammatory NF-κB signaling https://www.biorxiv.org/content/10.64898/2026.09.21.752888v1
September 23, 2026 at 1:30 AM
RNF213 M1-ubiquitinates damaged mitochondria to activate pro-inflammatory NF-κB signaling https://www.biorxiv.org/content/10.64898/2026.09.21.752888v1
RNF213 tags defective glycogen with ubiquitin and directs it to autophagy. This may prevent poorly branched sugar stores from accumulating as toxic polyglucosan clumps in brain cells. doi.org/hcjr58
Ubiquitin marks abnormal glycogen for destruction to protect the brain, study finds
Researchers at the University of Cambridge and the MRC Laboratory of Molecular Biology have discovered a previously unknown cellular defense system that protects the brain from abnormal glycogen accumulation, which is linked to severe neurological disorders.
phys.org
September 17, 2026 at 11:20 PM
RNF213 tags defective glycogen with ubiquitin and directs it to autophagy. This may prevent poorly branched sugar stores from accumulating as toxic polyglucosan clumps in brain cells. doi.org/hcjr58
How do cells remove abnormal glycogen?
Led by Matthew Yip, using mouse models, cell engineering & cryo-ET, Felix Randow's group found that RNF213 ubiquitylates aberrant glycogen to trigger autophagy.
https://mrclmb.ac.uk/news-events/articles/how-cells-clear-dysfunctional-glycogen/
#LMBResearch
Led by Matthew Yip, using mouse models, cell engineering & cryo-ET, Felix Randow's group found that RNF213 ubiquitylates aberrant glycogen to trigger autophagy.
https://mrclmb.ac.uk/news-events/articles/how-cells-clear-dysfunctional-glycogen/
#LMBResearch
September 16, 2026 at 8:46 AM
How do cells remove abnormal glycogen?
Led by Matthew Yip, using mouse models, cell engineering & cryo-ET, Felix Randow's group found that RNF213 ubiquitylates aberrant glycogen to trigger autophagy.
https://mrclmb.ac.uk/news-events/articles/how-cells-clear-dysfunctional-glycogen/
#LMBResearch
Led by Matthew Yip, using mouse models, cell engineering & cryo-ET, Felix Randow's group found that RNF213 ubiquitylates aberrant glycogen to trigger autophagy.
https://mrclmb.ac.uk/news-events/articles/how-cells-clear-dysfunctional-glycogen/
#LMBResearch
More evidence of glycogen ubiquitination:
Quality control of glycogen through direct ubiquitylation by RNF213
www.nature.com/articles/s41...
Quality control of glycogen through direct ubiquitylation by RNF213
www.nature.com/articles/s41...
Quality control of glycogen through direct ubiquitylation by RNF213 - Nature
Nature - Quality control of glycogen through direct ubiquitylation by RNF213
www.nature.com
September 15, 2026 at 11:23 PM
More evidence of glycogen ubiquitination:
Quality control of glycogen through direct ubiquitylation by RNF213
www.nature.com/articles/s41...
Quality control of glycogen through direct ubiquitylation by RNF213
www.nature.com/articles/s41...
Quality control of glycogen through direct ubiquitylation by RNF213 pubmed.ncbi.nlm.nih.gov/42744304/ #cryoem
September 16, 2026 at 10:27 AM
Quality control of glycogen through direct ubiquitylation by RNF213 pubmed.ncbi.nlm.nih.gov/42744304/ #cryoem
Contrôle qualité du glycogène par ubiquitination directe via RNF213
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Contrôle qualité du glycogène par ubiquitination directe via RNF213
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abestit.fr
September 16, 2026 at 3:12 AM
Contrôle qualité du glycogène par ubiquitination directe via RNF213
...
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Quality control of glycogen through direct ubiquitylation by RNF213
Nature, Published online: 15 September 2026; doi:10.1038/s41586-026-11139-6Quality control of glycogen through direct ubiquitylation by RNF213
Nature, Published online: 15 September 2026; doi:10.1038/s41586-026-11139-6Quality control of glycogen through direct ubiquitylation by RNF213
Quality control of glycogen through direct ubiquitylation by RNF213
Nature, Published online: 15 September 2026; doi:10.1038/s41586-026-11139-6Quality control of glycogen through direct ubiquitylation by RNF213
drwebdomain.blog
September 15, 2026 at 4:57 PM
Quality control of glycogen through direct ubiquitylation by RNF213
Nature, Published online: 15 September 2026; doi:10.1038/s41586-026-11139-6Quality control of glycogen through direct ubiquitylation by RNF213
Nature, Published online: 15 September 2026; doi:10.1038/s41586-026-11139-6Quality control of glycogen through direct ubiquitylation by RNF213
Toxoplasma gondii GRA66 prevents premature egress driven by the host phospholipase RARRES3, independently of RNF213 https://www.biorxiv.org/content/10.64898/2026.09.12.751112v1
September 15, 2026 at 12:16 PM
Toxoplasma gondii GRA66 prevents premature egress driven by the host phospholipase RARRES3, independently of RNF213 https://www.biorxiv.org/content/10.64898/2026.09.12.751112v1
Toxoplasma gondii GRA66 prevents premature egress driven by the host phospholipase RARRES3, independently of RNF213 https://www.biorxiv.org/content/10.64898/2026.09.12.751112v1
September 15, 2026 at 12:16 PM
Toxoplasma gondii GRA66 prevents premature egress driven by the host phospholipase RARRES3, independently of RNF213 https://www.biorxiv.org/content/10.64898/2026.09.12.751112v1
Interesting new RNF213 story from Mary Dickinson and Jörn Coers @coerslab.bsky.social showing xenophagy-independent role for RNF213 in cell autonomous immune defense: antimicrobial lysis of inclusions and host cell death after release.
RNF213-dependent lytic destruction of Chlamydia-containing vacuoles activates host cell death pathways | PNAS
The cytokine gamma-interferon promotes antimicrobial cell-autonomous immunity by inducing
hundreds of interferon-stimulated genes (ISGs). Among the...
www.pnas.org
August 29, 2026 at 5:03 PM
Interesting new RNF213 story from Mary Dickinson and Jörn Coers @coerslab.bsky.social showing xenophagy-independent role for RNF213 in cell autonomous immune defense: antimicrobial lysis of inclusions and host cell death after release.
What links B-cell receptor signaling with metabolism and development?
This study identifies RNF213 as a regulator of B-cell function, with its loss disrupting signaling, metabolism, and #BLymphocytes development.
#STTT #OpenAccess: doi.org/10.1038/s413...
This study identifies RNF213 as a regulator of B-cell function, with its loss disrupting signaling, metabolism, and #BLymphocytes development.
#STTT #OpenAccess: doi.org/10.1038/s413...
August 12, 2026 at 6:14 AM
What links B-cell receptor signaling with metabolism and development?
This study identifies RNF213 as a regulator of B-cell function, with its loss disrupting signaling, metabolism, and #BLymphocytes development.
#STTT #OpenAccess: doi.org/10.1038/s413...
This study identifies RNF213 as a regulator of B-cell function, with its loss disrupting signaling, metabolism, and #BLymphocytes development.
#STTT #OpenAccess: doi.org/10.1038/s413...
'Here we report that the evolutionary history of RNF213 is indicative of repeated adaptation to diverse pathogen target structures, especially in and around its newly identified CBM20 carbohydrate-binding domain, which we have resolved by cryo-EM.'
www.embopress.org/doi/full/10....
www.embopress.org/doi/full/10....
October 12, 2024 at 5:20 PM
'Here we report that the evolutionary history of RNF213 is indicative of repeated adaptation to diverse pathogen target structures, especially in and around its newly identified CBM20 carbohydrate-binding domain, which we have resolved by cryo-EM.'
www.embopress.org/doi/full/10....
www.embopress.org/doi/full/10....
RRIDs were included in this in bioRxiv paper. RRIDs improve reproducibility in scientific research. #methodsmatter #OpenResearch #STMpublishing
Interferon-gamma induced RNF213 targets nascent double membrane vesicles to inhibit coronavirus primary translation
Read the full paper: Interferon-gamma induced RNF213 targets nascent double membrane vesicles to inhibit coronavirus primary translation
doi.org
June 12, 2026 at 7:02 AM
RRIDs were included in this in bioRxiv paper. RRIDs improve reproducibility in scientific research. #methodsmatter #OpenResearch #STMpublishing
RRIDs were included in this in iScience paper. RRIDs improve reproducibility in scientific research. #OpenScience #OpenResearch #BetterScience
RNF213 isoform 2 restricts Zika virus through antiviral signaling and viral protein degradation
Read the full paper: RNF213 isoform 2 restricts Zika virus through antiviral signaling and viral protein degradation
doi.org
June 7, 2026 at 7:00 AM
RRIDs were included in this in iScience paper. RRIDs improve reproducibility in scientific research. #OpenScience #OpenResearch #BetterScience
RRIDs were included in this paper. We value the author's support of reproducibility. #methodsmatter #OpenScience #OpenScience
The Shigella flexneri effector IpaH1.4 facilitates RNF213 degradation and protects cytosolic bacteria against interferon-induced ubiquitylation
doi.org
December 3, 2025 at 8:00 AM
RRIDs were included in this paper. We value the author's support of reproducibility. #methodsmatter #OpenScience #OpenScience
The authors included RRIDs in their paper! We value the author's support of reproducibility. #methodsmatter #accelerateopenscience #accelerateopenscience
The Shigella flexneri effector IpaH1.4 facilitates RNF213 degradation and protects cytosolic bacteria against interferon-induced ubiquitylation
doi.org
November 12, 2025 at 8:00 AM
The authors included RRIDs in their paper! We value the author's support of reproducibility. #methodsmatter #accelerateopenscience #accelerateopenscience