iiinova — where your digital self keeps evolving

Qi Chen @qichen-lab.bsky.social · 12/09/2026

Hearty congratulations to Xudong on receiving an NIH K99 — one of our wishes during our lab anniversary trip has come true. Wishing you a golden future ahead!

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Qi Chen @qichen-lab.bsky.social · 26/07/2026

Adding to the intriguing story of Vault structures & their component Vault RNAs, we highlighted that Vault RNA-derived small RNAs (vtsRNAs) also bear biological functions: nature.com/articles/s41... It's Fascinating to see how nature always repurposes molecules for new functions! ♾

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Qi Chen @qichen-lab.bsky.social · 02/06/2026

After years of crystallization, in @natbiotech.nature.com, @zernickagoetz.bsky.social and I discuss the evolutionary origins of multicellularity & how physical constraints inevitably drive cellular self-organization. Harnessing these rules may help us better understand & engineer life rdcu.be/flTKa

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Qi Chen @qichen-lab.bsky.social · 20/01/2026

Perhaps the most puzzling part: We see a paradox: the rsRNA length shift is progressive⏳yet the global RNA profile shows an "Aging Cliff"📉. Cliff or Progression? Maybe the gradual shift is the forerunner—accumulating silently until it triggers the cliff. bsky.app/profile/qich...

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Qi Chen @qichen-lab.bsky.social · 20/01/2026

4/5 Crucially, beyond mouse data, we validated the sperm-head-specific rsRNA length shift signal in two independent human cohorts (longitudinal & cross-sectional). This suggests an evolutionarily conserved feature, which may stem from shared (enzymatic) mechanisms during aging.

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Qi Chen @qichen-lab.bsky.social · 20/01/2026

3/5 Perhaps the most surprising discovery: we see an age-dependent "Length Shift" in rsRNAs, exclusively found in sperm heads. Specifically, longer fragments accumulate while shorter ones decrease with age—a sign of altered RNA cleavage/processing efficiency (e.g., enzymatic).

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Qi Chen @qichen-lab.bsky.social · 20/01/2026

2/5 The first revelation: In mice, PANDORA-seq uncovers a sharp "Aging Cliff"📉in sperm RNA profiles at mid-life—a non-linear shift distinct from chronological age. Crucially, this cliff signal (genomic & mitochondrial tsRNAs/rsRNAs) is invisible to traditional small RNA-seq.

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Qi Chen @qichen-lab.bsky.social · 20/01/2026

1/5 It took us some time to connect the dots...now in @embojournal.org we use PANDORA-seq to start decoding the 'sperm RNA code of aging' We find a conserved rsRNA length shift that reflects aging in both mouse & human sperm, and an 'aging cliff' at mid-life🧵 link.springer.com/article/10.1...

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Qi Chen @qichen-lab.bsky.social · 25/12/2025

A road trip to Monument Valley and the wonders of the west, as an anniversary of lab’s 10th year operation…look forward to the journey ahead…

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Qi Chen @qichen-lab.bsky.social · 20/08/2025

Beyond inheritance, the model may also apply to cancer & neurodegeneration, where abnormal RNA structures could shape pathological cell states. Perhaps misfolded RNAs — not just amyloid proteins — are the central structural entity driving disease.

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Qi Chen @qichen-lab.bsky.social · 20/08/2025

Why the memory fades eventually - as often seen in epigenetic inheritance: Two potential exits: Active reset: when conditions normalize, condensates dissolve, RBPs shift, RNA refolds. Passive fade: cells with stress-memory may grow slower, and are outcompeted over generations.

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Qi Chen @qichen-lab.bsky.social · 20/08/2025

Memory propagation in cells — and across generations: Newly folded RNAs bind stress-linked RBPs to assemble new condensates, passed on during cell division. Even daughter cells never facing the original stress can inherit the RNA structural memory – and its stress-adapted traits.

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Qi Chen @qichen-lab.bsky.social · 20/08/2025

The heart of the hypothesis: copying RNA shape. Some RNAs can act as both template & catalyst, guiding new RNAs with the same sequence to fold the same way. RNA alone is unstable, but RBPs stabilize the template, & condensates boost RNA–RNA interactions—as a microreaction chamber

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Qi Chen @qichen-lab.bsky.social · 20/08/2025

The model starts with RNA folding energy & a multistable landscape. Under stress, RNA can adopt a new shape—and if RNA-binding proteins “lock” it in, that shape becomes a molecular memory of the stress. Think Waddington’s epigenetic landscape—but for RNA folding energy valleys.

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Qi Chen @qichen-lab.bsky.social · 20/08/2025

Perhaps our boldest hypothesis… we propose a model for RNA Structural Memory propagation in @natcellbio.nature.com where RNA conformation is reshaped by stress, locked by RBPs, copied prion-like in condensates & passed across generations—all without altering DNA rdcu.be/eBwPJ

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Qi Chen @qichen-lab.bsky.social · 01/05/2025

Very glad to see our Sequential Activation Hypothesis highlighted on the cover @cp-trendsbiochem.bsky.social , linking small RNA-TLR interactions to autoimmune disease mechanisms.

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Qi Chen @qichen-lab.bsky.social · 04/04/2025

We put together a step-by-step protocols for PANDORA-seq, now available in Nature Protocols @natprot.bsky.social , including the sample preparation for sperm, sperm heads; and the analyzing software SPORTS optimized for various types of small RNAs including tsRNAs, rsRNAs, and miRNAs. rdcu.be/egk1Z

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Qi Chen @qichen-lab.bsky.social · 16/02/2025

This idea is driven by advanced sncRNA sequencing (e.g. PANDORA-seq), uncovering an expanding universe of tsRNA/rsRNA/ysRNA & more www.nature.com/articles/s41... These sncRNAs go beyond RNAi, adopting aptamer-like roles by binding TLR7/8 to shape immune responses www.jbc.org/article/S002...

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Qi Chen @qichen-lab.bsky.social · 16/02/2025

TLR7/8 aren’t just triggered by viral RNAs, they can be potentially activated by a range of RNA resources: cell stress/death, RNA therapies, microbiome, and even dietary RNAs. Uncovering these diverse triggers may pave new paths for preventing/treating autoimmune diseases.

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Qi Chen @qichen-lab.bsky.social · 16/02/2025

How can abnormal small RNA biogenesis spark autoimmune disease? Our opinion @cp-trendsbiochem.bsky.social discuss a novel two-stage activation hypothesis that may explain why autoimmunity hits women harder, via small RNA-TLR7/8 interactions & augmented by autoantibodies. www.cell.com/trends/bioch...

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Qi Chen @qichen-lab.bsky.social · 30/11/2024

Starting this platform with the excursion to the historic village Shirakawa-go. #tRNA2024 conference at Kanazawa, Japan

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