A conserved post-transcriptional BMP2 switch in lung cells

An ultra‐conserved sequence in the bone morphogenetic protein 2 (BMP2) 3′ untranslated region (UTR) markedly represses BMP2 expression in non‐transformed lung cells. In contrast, the ultra‐conserved sequence stimulates BMP2 expression in transformed lung cells. The ultra‐conserved sequence functions as a post‐transcriptional cis‐regulatory switch. A common single‐nucleotide polymorphism (SNP, rs15705, +A1123C), which has been shown to influence human morphology, disrupts a conserved element within the ultra‐conserved sequence and altered reporter gene activity in non‐transformed lung cells. This polymorphism changed the affinity of the BMP2 RNA for several proteins including nucleolin, which has an increased affinity for the C allele. Elevated BMP2 synthesis is associated with increased malignancy in mouse models of lung cancer and poor lung cancer patient prognosis. Understanding the cis‐ and trans‐regulatory factors that control BMP2 synthesis is relevant to the initiation or progression of pathologies associated with abnormal BMP2 levels. J. Cell. Biochem. 110: 509–521, 2010. © 2010 Wiley‐Liss, Inc.