SCIENCE SIGNALING

Making Sense of EPO Receptors

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Science  13 Jun 2008:
Vol. 320, Issue 5882, pp. 1397
DOI: 10.1126/science.320.5882.1397c

Erythropoetin (EPO) signaling contributes to organ development, as well as to the differentiation of erythrocytes. The abundance of the EPO receptor (EPO-R) increases after removal of one lung (pneumonectomy) in dogs. In the same system, Zhang et al. report that the abundance of EPO-R appears to be regulated by the sense EPO-R transcript (sEPO-R), as well as by either the antisense transcript (asEPO-R) or by proteins encoded by two open reading frames (ORFs) within the antisense transcript. Both transcripts were detected in the normal canine lung; the abundance of sEPO-R increased modestly after pneumonectomy, whereas that of asEPO-R and EPO-R more than doubled. Coexpression of sEPO-R and asEPO-R increased the abundance of EPO-R in transfected human cells as compared to sEPO-R alone. The putative ORF1 protein was not needed to elevate EPO-R in transfected cells. In contrast, EPO-R production increased when a construct that included ORF2 and 300 base pairs 5′ of the ORF2 start site was cotransfected with sEPO-R; however, when the upstream region was not included, EPO-R abundance did not increase. The enhancing effect was restored by mutating the start codon of ORF2. The authors propose that asEPO-R has several regulatory elements, with the RNA having stimulatory effects and the ORF2 protein negative effects on EPO-R synthesis. — NRG

Proc. Natl. Acad. Sci. U.S.A. 105, 7612 (2008).

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