An Antisense Transcript toSMAD5Expressed in Fetal and Tumor Tissues

Abstract

SMAD5,a transducer of TGF-β/BMP inhibitory signals and a tumor suppressor candidate, localizes to the region of invariant loss in human myeloid neoplasms, on chromosome 5q31.1. Recent evidence indicates a gene-dosage effect along the TGF-β/BMP signaling pathways. We have identified a novel transcript designatedDAMS,whose 3′ exonic sequences contain in part an alternate 5′ exon ofSMAD5,in the antisense orientation. Expressed sequenced tags (ESTs) forDAMSare found in fetal tissues (heart, adrenal glands, and total fetus) and pancreatic tumor cDNA libraries. In contrast toSMAD5, DAMSexpression is not readily detectable in adult and fetal tissues. Semiquantitative PCR suggests that the stoichiometry betweenSMAD5andDAMStranscripts ranges between 15 and 120 in normal and malignant hematopoietic cells. The findings raise the possibility thatDAMSmay be a fail-safe mechanism for precise regulation ofSMAD5transcript levels that may be critical in maintaining normal homeostasis.