30S ribosomal protein S12 (uS12) (S12)

The RNA-binding S12 protein, primarily known as the 30S ribosomal protein S12 (rpsL) in bacteria and 40S ribosomal protein S12 (RPS12) in humans, is a fundamental structural and functional component of the small ribosomal subunit [1, 16]. In bacteria, S12 is a key regulator of translational accuracy, coordinating the selection of aminoacyl-tRNAs and maintaining the fidelity of the decoding process within the 30S subunit [6, 13]. It is the primary molecular target for the aminoglycoside antibiotic streptomycin, which binds at the interface of S12 and 16S rRNA to stabilize a 'closed' ribosome conformation, leading to lethal mRNA misreading and inhibition of protein synthesis [6, 9]. Mutations in the rpsL gene are clinically significant as they represent the most common mechanism for high-level streptomycin resistance in pathogens such as Mycobacterium tuberculosis [3, 7]. In humans, the ortholog RPS12 is involved in ribosome biogenesis and has recently emerged as a potential therapeutic target in oncology due to its role in promoting Wnt/Wingless secretion and its overproduction in malignancies like triple-negative breast cancer and colorectal cancer [5, 12, 19].

Other names

rpsLRPS12uS1240S ribosomal protein S12Small ribosomal subunit protein S12Ribosomal protein S12

Streptomycin binds to the 30S ribosomal subunit at the interface of the RNA-binding S12 protein and 16S rRNA, stabilizing the 'ram' (ribosome ambiguity) state; this reduces the selectivity of the decoding center, inducing the misreading of genetic code and the production of non-functional proteins [6, 7, 9, 13].