Selective expression of mRNA coding for the truncated form of erythropoietin receptor in hematopoietic cells and its decrease in patients with polycythemia vera.
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.
Chiba
S
S
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Japan.
Takahashi
T
T
Takeshita
K
K
Minowada
J
J
Yazaki
Y
Y
Ruddle
F H
FH
Hirai
H
H
D002460:Cell Line; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D011087:Polycythemia Vera / Q000097:blood* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D017467:Receptors, Erythropoietin / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D017467:Receptors, Erythropoietin