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
Proud to work with a brave team @cai000chen.bsky.social @jianchengyu.bsky.social Xudong Zhang & Tong Zhou—thinking fearlessly to bring this piece together.
In a time of uncertainty, may this idea be a seed for spring… We’ll see what evidence we and the community can bring, to confirm or refute…
In a time of uncertainty, may this idea be a seed for spring… We’ll see what evidence we and the community can bring, to confirm or refute…
August 20, 2025 at 10:29 AM
Proud to work with a brave team @cai000chen.bsky.social @jianchengyu.bsky.social Xudong Zhang & Tong Zhou—thinking fearlessly to bring this piece together.
In a time of uncertainty, may this idea be a seed for spring… We’ll see what evidence we and the community can bring, to confirm or refute…
In a time of uncertainty, may this idea be a seed for spring… We’ll see what evidence we and the community can bring, to confirm or refute…
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.
Proud of @jianchengyu.bsky.social and the team for thinking fearlessly to put the ideas together!
February 16, 2025 at 12:39 AM
Proud of @jianchengyu.bsky.social and the team for thinking fearlessly to put the ideas together!
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.