Conservation of Bmp2 post-transcriptional regulatory mechanisms.
Bone morphogenetic protein (BMP) orthologs from diverse species like flies and humans are functionally interchangeable and play key roles in fundamental processes such as dorso-ventral axis formation in metazoans. Because both transcriptional and post-transcriptional mechanisms play central roles in modulating developmental protein levels, we have analyzed the 3'-untranslated region (3'UTR) of the Bmp 2 gene. This 3'UTR is unusually long and is alternatively polyadenylated. Mouse, human, and dog mRNAs are 83-87% identical within this region. A 265-nucleotide sequence, conserved between mammals, birds, frogs, and fish, is present in Bmp2 but not Bmp4. The ability of AmphiBMP2/4, a chordate ortholog to Bmp2 and Bmp4, to align with this sequence suggests that its function may have been lost in Bmp4. Activation of reporter genes by the conserved region acts by a post-transcriptional mechanism. Mouse, human, chick, and zebrafish Bmp2 synthetic RNAs decay rapidly in extracts from cells not expressing Bmp2. In contrast, these RNAs are relatively stable in extracts from Bmp2-expressing cells. Thus, Bmp2 RNA half-lives in vitro correlate with natural Bmp2 mRNA levels. The fact that non-murine RNAs interact appropriately with the mouse decay machinery suggests that the function of these cis-regulatory regions has been conserved for 450 million years since the fish and tetrapod lineages diverged. Overall, our results suggest that the Bmp2 3'UTR contains essential regulatory elements that act post-transcriptionally.
Fritz
David T
DT
Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey (UMDNJ)-NJ Medical School, Newark, New Jersey 07101, USA.
Liu
Donglin
D
Xu
Junwang
J
Jiang
Shan
S
Rogers
Melissa B
MB
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000737:chemistry* / Q000235:genetics*; D002130:Calcium Phosphates / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002645:Chickens; D003001:Cloning, Molecular; D006224:Cricetinae; D004285:Dogs; D019143:Evolution, Molecular; D020224:Expressed Sequence Tags; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D026723:Polyadenylation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015027:Zebrafish
D020413:3' Untranslated Regions; C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002130:Calcium Phosphates; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C020243:calcium phosphate; D008156:Luciferases; D012260:Ribonucleases