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Joe Yesselman

@josephyesselman.bsky.social
248 followers 121 following 26 posts

RNA structural biologist, developing RNA-based nanomachines for therapeutic and biosensing applications. yesselmanlab.com

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Joe Yesselman @josephyesselman.bsky.social · 11/08/2026
New preprint from the lab! Riboswitches toggle by rearranging base pairs. Can you get the same toggling without changing the secondary structure? Turns out yes. We designed a minimal modular RNA that forms or breaks a tertiary contact in response to ligand binding. www.biorxiv.org/content/10.6...
biorxiv.org
Single-base substitutions switch RNA tertiary allostery between positive and negative coupling.
Riboswitches regulate gene expression in response to ligand binding, remodeling their secondary structure to terminate transcription or block translation. This innate switching has driven efforts to r...
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Joe Yesselman @josephyesselman.bsky.social · 17/07/2026
All of this holds under in vivo-like probing conditions too (37°C, 2 min), so it is not an artifact of the room temp protocol. Great work by Sanduni Deenalattha, Chris Jurich, and the whole team!
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Joe Yesselman @josephyesselman.bsky.social · 17/07/2026
And this can be used directly to improve modeling. Adding a single reactivity-derived distance constraint to Rosetta recovered native A-G geometries that unconstrained modeling could not predict.
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Joe Yesselman @josephyesselman.bsky.social · 17/07/2026
The result we were most excited about is that reactivity correlates directly with 3D conformation. In noncanonical pairs, especially A-G, it tracks the phosphate-to-phosphate distance closely enough to tell distinct base pair geometries apart.
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Joe Yesselman @josephyesselman.bsky.social · 17/07/2026
We also found ~14.5% of noncanonical pairs are as protected as WC pairs, through real H-bonding and reduced solvent accessibility. So low reactivity nucleotide does not mean a canonical pair.
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Joe Yesselman @josephyesselman.bsky.social · 17/07/2026
Reactivity of flanking pairs is not explained by static distortion. It tracks junction asymmetry, the stacking environment, and whether the neighbors are purines or pyrimidines.
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Joe Yesselman @josephyesselman.bsky.social · 17/07/2026
The first thing we found is that reactivity is not two clean populations. It is a continuum spanning four orders of magnitude, and about 10% of Watson-Crick and non-WC nucleotides overlap. If you are setting a threshold for paired vs unpaired you could be throwing away data.
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Joe Yesselman @josephyesselman.bsky.social · 17/07/2026
New paper! While it has been known that DMS encodes more information than secondary structure, it has never really been characterized. So we did the first large study to look: 7,500 RNAs, all with known 3D structures. We found a lot of cool structural relationships. doi.org/10.1093/nar/...
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Joe Yesselman @josephyesselman.bsky.social · 12/12/2024
Being in the same tweet as Olke Uhlenbeck is a true honor. Thank you @jhdcate.bsky.social
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Joe Yesselman @josephyesselman.bsky.social · 12/12/2024
Excited to announce a new collaborative preprint about a structural concept 'local stability compensation'. This states structurally important motifs must be flanked by more stable helices. We observe this effect natural occurring RNAs and experimentally evaluate it. www.biorxiv.org/content/10.1...
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Joe Yesselman @josephyesselman.bsky.social · 03/12/2024
It's great to see the latest RNA puzzles paper has come out. www.nature.com/articles/s41... Its a must-read for those interested in RNA structure prediction!
nature.com
RNA-Puzzles Round V: blind predictions of 23 RNA structures - Nature Methods
The results of the Fifth RNA-Puzzles contest highlights advances in RNA three-dimensional structure prediction and uncovers new insights into RNA folding and structure.
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Joe Yesselman @josephyesselman.bsky.social · 29/11/2024
Hi @incarnatolab.bsky.social thanks very much. Yes we ran this already and are processing now. There are many interesting things to checkout.
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Joe Yesselman @josephyesselman.bsky.social · 25/11/2024
@rodrigo-reis.bsky.social We are doing that right now. I totally agree.
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Joe Yesselman @josephyesselman.bsky.social · 25/11/2024
@gallardo-seq.bsky.social yes, I absolutely agree.
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Joe Yesselman @josephyesselman.bsky.social · 25/11/2024
Our results provide a quantitative framework for interpreting DMS reactivity patterns in RNA. This enables more sophisticated structure prediction algorithms that consider local sequence context, non-canonical interactions, and three-dimensional features - moving beyond simple base-pair predictions.
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Joe Yesselman @josephyesselman.bsky.social · 25/11/2024
Most significantly, we discover that DMS reactivity correlates strongly with atomic distances in non-canonical base pairs. These quantitative relationships demonstrate that DMS chemical mapping data encodes detailed information about RNA 3D structure.
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Joe Yesselman @josephyesselman.bsky.social · 25/11/2024
Our results provide a quantitative framework for interpreting DMS reactivity patterns in RNA. This enables more sophisticated structure prediction algorithms that consider local sequence context, non-canonical interactions, and three-dimensional features - moving beyond simple base-pair predictions.
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Joe Yesselman @josephyesselman.bsky.social · 25/11/2024
Our results provide a quantitative framework for interpreting DMS reactivity patterns in RNA. This enables more sophisticated structure prediction algorithms that consider local sequence context, non-canonical interactions, and three-dimensional features - moving beyond simple base-pair predictions.
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Joe Yesselman @josephyesselman.bsky.social · 25/11/2024
Most significantly, we discover that DMS reactivity correlates strongly with atomic distances in non-canonical base pairs. These quantitative relationships demonstrate that DMS chemical mapping data encodes detailed information about RNA 3D structure.
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Joe Yesselman @josephyesselman.bsky.social · 25/11/2024
We find that 11% of non-Watson-Crick nucleotides show protection from DMS similar to Watson-Crick pairs. This protection stems from hydrogen bonding and reduced solvent accessibility. Sequence context can alter reactivity up to 100-fold in specific non-canonical pairs.
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Joe Yesselman @josephyesselman.bsky.social · 25/11/2024
We analyzed flanking WC pairs and found structural features that determine their DMS reactivity. A-U pairs are 19-fold more reactive than G-C pairs, purine neighbors increase reactivity, and junction asymmetry correlates with higher reactivity.
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Joe Yesselman @josephyesselman.bsky.social · 25/11/2024
Analysis of our comprehensive dataset reveals DMS reactivity exists on a continuous spectrum rather than discrete states. We observe ~10% overlap between Watson-Crick and non-Watson-Crick nucleotides, demonstrating that simple reactivity thresholds cannot reliably determine base-pairing status.
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Joe Yesselman @josephyesselman.bsky.social · 25/11/2024
To correlate DMS reactivity with RNA structure, we built a massive library of 7,500 RNA constructs containing multiple junctions with known 3D structures. Our measurements are highly reproducible (R²=0.99), span four orders of magnitude, and reveal that RNA motifs have unique DMS profiles.
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Joe Yesselman @josephyesselman.bsky.social · 25/11/2024
🧬 Excited to share our new preprint! DMS chemical mapping, a key technique for studying RNA structure. Everyone assumes low DMS reactivity = Watson-Crick , high = non-WC. However, analyzing 7,500 RNA structures containing known 3D structures reveals it's not that simple. doi.org/10.1101/2024...
biorxiv.org
A quantitative framework for structural interpretation of DMS reactivity
Dimethyl sulfate (DMS) chemical mapping is widely used for probing RNA structure, with low reactivity interpreted as Watson-Crick (WC) base pairs and high reactivity as unpaired nucleotides. Despite i...
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Joe Yesselman @josephyesselman.bsky.social · 22/11/2024
@incarnatolab.bsky.social Same. Thanks for the shoutout. It's nice to see you here.
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Joe Yesselman @josephyesselman.bsky.social · 19/11/2024
I hope this place is more positive and science-friendly than Twitter. I look forward to chatting about awesome science.
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