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.
Jiang
Shan
S
Department of Biochemistry and Molecular Biology, UMDNJ-NJMS, Newark, New Jersey 07101, USA.
Fritz
David T
DT
Rogers
Melissa B
MB
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D040901:Proteomics; D012323:RNA Processing, Post-Transcriptional; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020413:3' Untranslated Regions; D055396:Bone Morphogenetic Protein 2; D017931:DNA Primers