Post-transcriptional regulation of the cell surface expression of glycophorins A, B, and E.

Abstract GYPA, GYPB, and GYPE represent a small gene family localized on chromosome 4q28-q31 that encodes the major red cell membrane glycophorins, GPA and GPB, and a new but as yet uncharacterized glycoprotein, GPE. There are 3-4 times more copies of GPA as compared with GPB on human erythrocytes (10(6) versus 2 x 10(5) copies/cell), whereas GPE is absent or poorly represented. Whether these quantitative differences reflect a transcriptional or post-transcriptional regulation was investigated. We found the functional activities of the glycophorin promoters to be similar, as shown by DNase I footprinting, gel retardation, methylation interference, and deletion analysis. Run-on analysis indicated that the transcription rate of each glycophorin gene in K562 cells was also very similar. However, large differences in mRNA decay were found in actinomycin-treated K562 cells. GPA transcripts were very stable (at least 24 h), whereas GPB transcripts were severely reduced after 17 h. The GPE transcripts were barely detectable and disappeared completely after 1 h. These results suggest that a difference in stability of the GPA, GPB, and GPE transcripts rather than a transcriptional regulation may predominantly account for the different levels of glycophorin expression on erythrocytes.