Qi Chen

FUSION: a family-level integration approach for robust differential analysis of small non-coding RNAs AbstractMotivation. Beyond well-studied microRNAs, noncanonical small non-coding RNAs (sncRNAs) derived from longer parental templates such as tRNAs, rRNAs

After developing PANDORA-seq to reveal hidden small RNAs (e.g., tsRNA, rsRNA) and SPORTS to annotate them, we now expand our toolchain with Tong Zhou lab: introducing FUSION, a tool that robustly interprets small RNA changes even in small or 1-on-1 datasets.
academic.oup.com/bioinformati...

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…

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.

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.

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.

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

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.

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

Our 🌷 May 🌷 issue is online with a broad range of article topics and formats!

In their Opinion article (on the cover, too!), @qichen-lab.bsky.social and colleagues describe the interactions between small ncRNAs and Toll-like receptors.

Find the issue here: www.cell.com/trends/bioch...

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.

Optimized identification and characterization of small RNAs with PANDORA-seq - Nature Protocols This Protocol describes optimized procedures for purification and sequencing of small noncoding RNAs from a variety of samples to characterize these diverse RNA species and map them to the parental RNAs from which they originate.

#NewNProt for #genomewide characterization of a diverse set of #smallnoncodingRNAs in cells and tissues

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

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...

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.

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...

go.bsky.app/QkSL6S5

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