Chiba S, Takahashi T, Takeshita K, Minowada J, Yazaki Y, Ruddle F H, Hirai H
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Japan.
Blood. 1997 Jul 1;90(1):97-104.
The mRNA encoding full-length erythropoietin (EPO) receptor (EPOR-F) comprises exons I through VIII. Another membrane-bound EPOR (EPOR-T) isoform has a truncated cytoplasmic region and is encoded by the mRNA containing unspliced intron VII (EPOR-T mRNA). EPOR-T is believed to have a dominantly negative function against EPOR-F. We show that EPOR-T mRNA is markedly decreased in the blood cells of patients with polycythemia vera (PV). We also show that EPOR-T mRNA is not detected in erythroid/megakaryocytic leukemia cell lines, but is expressed in nonerythroid/nonmegakaryocytic lines, suggesting the presence of a cell type-specific system by which intron VII of the EPOR transcript is spliced. Deregulation of this splicing system in early hematopoietic progenitors possibly explains the profound decrease in EPOR-T mRNA and consequent pathophysiology of PV.
编码全长促红细胞生成素（EPO）受体（EPOR-F）的信使核糖核酸（mRNA）由外显子I至VIII组成。另一种膜结合型EPO受体（EPOR-T）亚型具有截短的胞质区域，由包含未剪接内含子VII的mRNA编码（EPOR-T mRNA）。据信EPOR-T对EPOR-F具有显性负功能。我们发现，真性红细胞增多症（PV）患者血细胞中的EPOR-T mRNA显著减少。我们还发现，在红系/巨核细胞白血病细胞系中未检测到EPOR-T mRNA，但在非红系/非巨核细胞系中表达，这表明存在一种细胞类型特异性系统，通过该系统EPOR转录本的内含子VII被剪接。早期造血祖细胞中这种剪接系统的失调可能解释了EPOR-T mRNA的显著减少以及PV随之而来的病理生理学。
