40S

The 40S ribosomal subunit is the small subunit of eukaryotic ribosomes. Along with the 60S subunit, it forms the 80S ribosome that synthesizes proteins in the cytoplasm. The designation 40S reflects its sedimentation coefficient in Svedberg units during ultracentrifugation.

The 40S subunit comprises about 18S ribosomal RNA (rRNA) and around 33 ribosomal proteins, designated as RPS proteins. The 18S rRNA provides the decoding center and the mRNA-binding platform, while the surrounding proteins stabilize structure and participate in interactions with initiation factors and tRNA during translation.

In translation initiation, the 40S subunit binds to mRNA and, with initiation factors, scans for the start codon. It forms the pre-initiation complex with other components such as eIF2-GTP-tRNAiMet and various initiation factors; recruitment of mRNA via the cap-binding complex eIF4F helps assemble the initiation complex. Upon start codon recognition, the 60S subunit joins to form the active 80S ribosome, and elongation proceeds on the assembled complex.

Biogenesis of the 40S subunit begins in the nucleolus, where the 18S rRNA is transcribed as part of the 18S-5.8S-28S rRNA gene cluster by RNA polymerase I and undergoes processing. Ribosomal proteins are synthesized in the cytosol and imported into the nucleus, where they assemble with the 18S rRNA to form pre-40S particles. Mature 40S subunits are exported to the cytoplasm for final maturation and participation in translation.

Clinical relevance: Mutations or haploinsufficiency in RPS genes, notably RPS19, can cause Diamond-Blackfan anemia and other ribosomopathies. Such defects disrupt ribosome biogenesis and can activate p53 pathways, contributing to disease pathology and cancer risk.