STRUCTURE AND FUNCTION OF RIBOSOMAL PROTEIN-S4 GENES ON THE HUMAN ANDMOUSE SEX-CHROMOSOMES

The human sex-linked genes RPS4X and RPS4Y encode distinct isoforms of ribosomal protein S4. Insufficient expression of S4 may play a role i n the development of Turner syndrome, the complex human phenotype asso ciated with monosomy X. In mice, the S4 protein is encoded by an X-lin ked gene, Rps4, and is identical to human S4X; there is no mouse Y hom olog. We report here the organization of the human PPS4X and PPS4Y and mouse Rps4 genes. Each gene comprises seven exons; the positions of i ntrons are conserved. The 5' Hanking sequences of human RPS4X and mous e Rps4 are very similar, while RPS4Y diverges shortly upstream of the transcription start site. In chickens, S4 is encoded by a single gene that is not sex linked. The chicken protein differs from human S4X by four amino acid substitutions, all within a region encoded by a single exon. Three of the four substitutions are also present in human S4Y, suggesting that the chicken S4 gene may have arisen by recombination b etween S4X- and S4Y-like sequences. Using isoform-specific antisera, w e determined that human S4X and S4Y are both present in translationall y active ribosomes. S4Y is about 10 to 15% as abundant as S4X in ribos omes from normal male placental tissue and 46,XY cultured cells. In 49 ,XYYYY cells, S4Y is about half as abundant as S4X. In 49,XXXXY cells, S4Y is barely detectable. These results bear on the hypothesized role of S4 deficiency in Turner syndrome.