Protein Synthesis: Translation and Post‑Translational Modifications
Concept Name
Translation
Genetic Loci
Ribosomal protein genes: RPS19 (19q13.2) – mutations cause Diamond‑Blackfan anemia. tRNA genes are scattered across multiple chromosomes. eIF2α (EIF2S1 on 14q23.3).
Intracellular Cascade
mTORC1 pathway phosphorylates 4E‑BP1, releasing eIF4E to initiate translation. The integrated stress response (ISR) involves eIF2α phosphorylation by kinases (GCN2, PERK, PKR, HRI), which inhibits global translation while upregulating ATF4.
Required Cofactors
GTP is required for elongation factors (EF‑Tu, EF‑G). Mg²⁺ stabilizes ribosome structure. ATP is required for aminoacyl‑tRNA synthetases.
Histology Stains
Immunohistochemistry for ribosomal protein S6 (phosphorylated form) marks active translation. Silver staining (AgNOR) highlights nucleolar organizing regions active in ribosome biogenesis.
EM Findings
Polysomes appear as clusters of ribosomes along a single mRNA strand. Rough endoplasmic reticulum studded with ribosomes is prominent in secretory cells (e.g., pancreatic acinar cells).
Knockout Phenotype
Homozygous deletion of eIF2α in mice is perinatally lethal. Conditional knockout of RPS6 in hepatocytes leads to impaired liver regeneration.
Specific Toxins
Puromycin causes premature chain termination by mimicking aminoacyl‑tRNA. Cycloheximide inhibits translocation by eukaryotic ribosomes. Diphtheria toxin ADP‑ribosylates EF‑2, blocking translocation. Ricin depurinates 28S rRNA.