Panos Poulis (currently in DE)
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panos-poulis.bsky.social
Panos Poulis (currently in DE)
@panos-poulis.bsky.social
Joint @maxplanck.de & @weizmanninstitute.bsky.social fellow
mRNA recoding in cancer and RNA-based therapeutics, watching one molecule at a time
PhD @mpi-nat.bsky.social
September 28, 2026 at 12:14 PM
6/6
This work is the combined effort of several people! Huge thanks to the amazing co-first author Giovanni Robecchi, Arina Kurochkina, @michelefelletti.bsky.social and Marina Rodnina, as well as to the editors of @natcomms.nature.com and the reviewers!
September 28, 2026 at 10:16 AM
5/6
The take-home message is a double-sieve principle: RNA modifications may change the ''chemical'' glossary that the ribosome uses to synthesize a protein. Alongside immunogenicity and expression, translation fidelity should be evaluated when designing mRNA therapeutics.
September 28, 2026 at 10:16 AM
4/6
The fix is in the sequence. Swapping slippery codons for the synonymous non-slippery ones eliminates the effect. Avoiding downstream codons that start with C helps too.
September 28, 2026 at 10:16 AM
3/6
Mechanism: Frameshifting happens through a "hungry" P-site stalling. While the ribosome waits for the next tRNA, m1Ψ weakens codon–anticodon pairing and favors a frameshifting-prone tRNA state.
September 28, 2026 at 10:16 AM
2/6
Using human cell reporters, a reconstituted translation system and single-molecule FRET, we found that m1Ψ raises +1 frameshifting on slippery motifs. The effect is low-level (~1–3%) and sequence-dependent.
September 28, 2026 at 10:16 AM