# Vocabulary Back to [[Ribosome Pausing and Cotranslational Folding]] · Evidence: [[Research and Evidence]] ## Translation basics - **Ribosome:** the RNA–protein machine that reads mRNA and links amino acids into a protein. Bacteria have 70S ribosomes, eukaryotes 80S ("S" is a sedimentation unit). Roughly 20–30 nm across. - **mRNA / codon:** messenger RNA carries the gene's sequence; each three-base codon specifies one amino acid or a stop. - **tRNA:** adaptor RNA that carries an amino acid and pairs with a codon. Cells hold different amounts of each tRNA, which affects decoding speed. - **Elongation:** the step where the ribosome adds amino acids one at a time (about 5–6 aa/s in mammalian cells, faster in bacteria). - **Nascent chain:** the protein while it is still being made and attached to the ribosome. - **Exit tunnel:** the channel in the large ribosomal subunit through which the nascent chain emerges. It holds roughly 30–40 residues, and some folding starts inside it. ## Speed and pausing - **Synonymous codons:** different codons for the same amino acid (e.g., six codons for leucine). Changing one is a **synonymous** or **"silent" mutation**, silent in sequence but not always in effect. - **Codon usage bias:** organisms use synonymous codons unevenly. - **Codon optimality:** how efficiently a codon is decoded, given tRNA supply and pairing. "Rare" or "non-optimal" codons tend to be slower. - **Wobble pairing:** non-standard base pairing at the codon's third position; often slower to decode. - **Ribosome pausing:** a brief, often programmed slowdown at a specific site. Can aid folding, membrane targeting or protein assembly. - **Ribosome stalling:** a prolonged arrest. Usually harmful, though some stalling peptides (SecM, TnaC) stall on purpose as sensors or regulators. The post blurs pausing and stalling. - **Ribosome collision / disome:** a trailing ribosome runs into a stalled one; a two-ribosome complex is a disome. - **No-go decay (NGD):** mRNA cleavage triggered by stalled or collided ribosomes. - **Ribosome-associated quality control (RQC):** the pathway that rescues stalled ribosomes and degrades the incomplete protein. ## Folding - **Protein folding:** the chain adopting its working 3D shape. - **Anfinsen's dogma:** the sequence alone encodes the native structure (true for many small proteins refolded in a test tube). - **Cotranslational folding:** folding that begins while the protein is still being synthesized, domain by domain. - **Kinetic trap / misfolding:** a wrong, stable shape the protein gets stuck in. - **Chaperones:** proteins that help others fold (trigger factor in bacteria; NAC, Hsp70s and the TRiC chaperonin in eukaryotes). - **Domain:** an independently folding unit of a protein. Pauses near domain boundaries can give a domain time to fold before the next one emerges. ## Methods - **Ribosome profiling (Ribo-seq):** sequencing the mRNA fragments protected by ribosomes to map their positions genome-wide at codon resolution. - **Disome-seq:** the same, for collided ribosome pairs. - **Pulse-chase:** label new proteins briefly and follow them over time. - **Optical tweezers:** laser traps that pull on a single nascent chain to watch it fold. - **Force-profile analysis:** using arrest peptides as force sensors to detect when a nascent chain folds. - **Cryo-EM:** electron microscopy of frozen samples for near-atomic structures, including ribosome–nascent chain complexes. ## Engineering - **Codon optimization:** rewriting a gene with "preferred" codons to boost expression in a host. - **Codon harmonization:** rewriting a gene to keep the original slow/fast pattern in the new host. - **tAI / CAI:** tRNA Adaptation Index and Codon Adaptation Index, scores of how well a gene's codons match the host's tRNA pool or highly expressed genes. - **MFE (minimum free energy):** a predicted measure of how stable an mRNA's folded structure is; stable structure can slow the ribosome. ## AI and X terms in the post - **Claude:** Anthropic's AI model family. "Claude Opus 5.5", named in the video, is unconfirmed ⚠️. - **Jev ("JEV"):** TypeSafe's "System One" model that returns typed decisions (choice, score or "noul") rather than text. - **"Noul":** TypeSafe's term for a "none of the above" decision output. - **Structure prediction / "Big" mode / FlashPairformer:** Anthropic's Sep 2026 work making AlphaFold-style models faster and able to handle very large complexes such as a ribosome. - **X Article / long post:** X features for long-form writing; the post quotes the author's own Article. - **Engagement bait:** hooks and calls to action ("bookmark, RT and follow") designed to drive interactions rather than inform.