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A Polymorphism in a Conserved Posttranscriptional Regulatory Motif Alters Bone Morphogenetic Protein 2 (BMP2) RNA:Protein Interactions

Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07101

Address all correspondence and requests for reprints to: Melissa B. Rogers, Biochemistry and Molecular Biology (MSB E627), University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 South Orange Avenue, P.O. Box 1709, Newark, New Jersey 07101-1709. E-mail: rogersmb{at}umdnj.edu.

The bone morphogenetic protein (BMP)2 gene has been genetically linked to osteoporosis and osteoarthritis. We have shown that the 3'-untranslated regions (UTR) of BMP2 genes from mammals to fishes are extraordinarily conserved. This indicates that the BMP2 3'-UTR is under stringent selective pressure. We present evidence that the conserved region is a strong posttranscriptional regulator of BMP2 expression. Polymorphisms in cis-regulatory elements have been proven to influence susceptibility to a growing number of diseases. A common single nucleotide polymorphism (SNP) disrupts a putative posttranscriptional regulatory motif, an AU-rich element, within the BMP2 3'-UTR. The affinity of specific proteins for the rs15705 SNP sequence differs from their affinity for the normal human sequence. More importantly, the in vitro decay rate of RNAs with the SNP is higher than that of RNAs with the normal sequence. Such changes in mRNA:protein interactions may influence the posttranscriptional mechanisms that control BMP2 gene expression. The consequent alterations in BMP2 protein levels may influence the development or physiology of bone or other BMP2-influenced tissues.

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				D. Liu, D. T. Fritz, M. B. Rogers, and A. J. Shatkin Species-specific cis-Regulatory Elements in the 3'-Untranslated Region Direct Alternative Polyadenylation of Bone Morphogenetic Protein 2 mRNA J. Biol. Chem., October 17, 2008; 283(42): 28010 - 28019. [Abstract] [Full Text] [PDF]