Ribosomal protein uS12 (uS12)

Ribosomal protein uS12 is a universally conserved component of the small ribosomal subunit (30S in bacteria and 40S in eukaryotes) and plays a pivotal role in maintaining the fidelity of protein synthesis. Located at the decoding center of the ribosome, uS12 monitors the accuracy of codon-anticodon interactions, ensuring that the correct aminoacyl-tRNA is selected during translation. In bacteria, uS12 (encoded by the rpsL gene) is a well-characterized target for the aminoglycoside antibiotic streptomycin, which binds to the decoding site and induces misreading of the genetic code. Mutations in uS12 are a common mechanism of high-level streptomycin resistance, often leading to 'hyper-accurate' ribosomes that exhibit reduced translation rates. In humans, the uS12 homolog is known as RPS23; mutations in this protein have been linked to rare ribosomopathies, such as brachycephaly, trichomegaly, and developmental delay (BTDD). Additionally, uS12 has been implicated in extra-ribosomal functions, including cell competition and stress response signaling, and its expression levels are altered in certain cancers.

Other names

30S ribosomal protein S1240S ribosomal protein S23rpsLRPS23S12Small ribosomal subunit protein uS12

Streptomycin binds to the decoding center of the small ribosomal subunit, interacting with 16S rRNA and the uS12 protein to stabilize the closed conformation of the ribosome and promote translational misreading. Dityromycin binds directly to uS12, inhibiting translocation by trapping elongation factor G (EF-G) on the ribosome.