Decrease in hnRNP A/B expression during erythropoiesis mediates a pre-mRNA splicing switch

Victor C. Hou, Robert Lersch, Sherry L. Gee, Julie L. Ponthier, Annie J. Lo, Michael Wu, Chris W. Turck, Mark Koury, Adrian R. Krainer, Akila Mayeda, John G. Conboy

研究成果: Article

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A physiologically important alternative pre-mRNA splicing switch, involving activation of protein 4.1R exon 16 (E16) splicing, is required for the establishment of proper mechanical integrity of the erythrocyte membrane during erythropoiesis. Here we identify a conserved exonic splicing silencer element (CE16) in E16 that interacts with hnRNP A/B proteins and plays a role in repression of E16 splicing during early erythropoiesis. Experiments with model pre-mRNAs showed that CE16 can repress splicing of upstream introns, and that mutagenesis or replacement of CE16 can relieve this inhibition. An affinity selection assay with biotinylated CE16 RNA demonstrated specific binding of hnRNP A/B proteins. Depletion of hnRNP A/B proteins from nuclear extract significantly increased E16 inclusion, while repletion with recombinant hnRNP A/B restored E16 silencing. Most importantly, differentiating mouse erythroblasts exhibited a stage-specific activation of the E16 splicing switch in concert with a dramatic and specific down-regulation of hnRNP A/B protein expression. These findings demonstrate that natural developmental changes in hnRNP A/B proteins can effect physiologically important switches in pre-mRNA splicing.

元の言語English
ページ(範囲)6195-6204
ページ数10
ジャーナルEMBO Journal
21
発行部数22
DOI
出版物ステータスPublished - 15-11-2002

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Hou, V. C., Lersch, R., Gee, S. L., Ponthier, J. L., Lo, A. J., Wu, M., Turck, C. W., Koury, M., Krainer, A. R., Mayeda, A., & Conboy, J. G. (2002). Decrease in hnRNP A/B expression during erythropoiesis mediates a pre-mRNA splicing switch. EMBO Journal, 21(22), 6195-6204. https://doi.org/10.1093/emboj/cdf625