Qi Chen
@qichen-lab.bsky.social
Associate Professor, University of Utah | sperm RNA-mediated epigenetic inheritance, embryo development, small RNAs, RNA modifications & diseases | http://qichen-lab.info
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.
Perhaps misfolded RNAs — not just amyloid proteins — are the central structural entity driving disease.
August 20, 2025 at 10:29 AM
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.
Perhaps misfolded RNAs — not just amyloid proteins — are the central structural entity driving disease.
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.
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.
August 20, 2025 at 10:29 AM
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.
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.
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.
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.
August 20, 2025 at 10:29 AM
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.
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.
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
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
August 20, 2025 at 10:29 AM
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
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
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.
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.
August 20, 2025 at 10:29 AM
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.
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.
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
rdcu.be/eBwPJ
August 20, 2025 at 10:29 AM
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
rdcu.be/eBwPJ
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.
May 1, 2025 at 5:21 PM
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.
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
April 4, 2025 at 6:10 AM
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
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...
These sncRNAs go beyond RNAi, adopting aptamer-like roles by binding TLR7/8 to shape immune responses
www.jbc.org/article/S002...
February 16, 2025 at 12:39 AM
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...
These sncRNAs go beyond RNAi, adopting aptamer-like roles by binding TLR7/8 to shape immune responses
www.jbc.org/article/S002...
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.
Uncovering these diverse triggers may pave new paths for preventing/treating autoimmune diseases.
February 16, 2025 at 12:39 AM
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.
Uncovering these diverse triggers may pave new paths for preventing/treating autoimmune diseases.
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...
www.cell.com/trends/bioch...
February 16, 2025 at 12:39 AM
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...
www.cell.com/trends/bioch...
