Alternative polyadenylation signals and promoters act in concert to control tissue-specific expression of the Opitz Syndrome gene MID1.
BACKGROUND
Mutations in the X-linked MID1 gene are responsible for Opitz G/BBB syndrome, a malformation disorder of developing midline structures. Previous Northern blot analyses revealed the existence of at least three MID1 transcripts of differing lengths.


RESULTS
Here we show that alternative polyadenylation generates the size differences observed in the Northern blot analyses. Analysis of EST data together with additional Northern blot analyses proved tissue-specific usage of the alternative polyadenylation sites. Bioinformatic characterization of the different 3'UTRs of MID1 revealed numerous RNA-protein interaction motifs, several of which turned out to be conserved between different species. Furthermore, our data suggest that mRNA termination at different polyadenylation sites is predetermined by the choice of alternative 5'UTRs and promoters of the MID1 gene, a mechanism that efficiently allows synergistic function of 5' and 3'UTRs.


CONCLUSIONS
MID1 expression is tightly regulated through concerted action of alternative promoters and alternative polyadenylation signals both during embryonic development and in the adult.
Winter
Jennifer
J
Max-Planck Institute for Molecular Genetics, Berlin-Dahlem, Germany. winter@molgen.mpg.de
Kunath
Melanie
M
Roepcke
Stefan
S
Krause
Sven
S
Schneider
Rainer
R
Schweiger
Susann
S
D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D017124:Conserved Sequence; D020224:Expressed Sequence Tags; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008868:Microtubule Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D009928:Organ Specificity; D026723:Polyadenylation / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics*; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D008868:Microtubule Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C109052:MID1 protein, human; D044767:Ubiquitin-Protein Ligases