An antisense transcript to SMAD5 expressed in fetal and tumor tissues

SMAD5, a transducer of TGF-beta/BMP inhibitory signals and a tumor suppress or candidate, localizes to the region of invariant loss in human myeloid ne oplasms, on chromosome 5q31.1. Recent evidence indicates a gene-dosage effe ct along the TGF-beta/BMP signaling pathways. We have identified a novel tr anscript. designated DAMS, whose 3' exonic sequences contain in part an alt ernate 5' exon of SMAD5, in the antisense orientation. Expressed sequenced tags (ESTs) for DAMS are found in fetal tissues (heart, adrenal glands, and total fetus) and pancreatic tumor cDNA libraries. In contrast to SMAD5, DA MS expression is not readily detectable in adult and fetal tissues. Semiqua ntitative PCR suggests that the stoichiometry between SMAD5 and DAMS transc ripts ranges between 15 and 120 in normal and malignant hematopoietic cells . The findings raise the possibility that DAMS may be a fail-safe mechanism for precise regulation of SMAD5 transcript levels that may be critical in maintaining normal homeostasis. (C) 1999 Academic Press.