mRNA recoding in cancer and RNA-based therapeutics, watching one molecule at a time
PhD @mpi-nat.bsky.social
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!
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!
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.
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.
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.
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.
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.
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.
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.
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.