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Document Version Version Comment Date Status
225768.0 [No comment] 15.06.2005 11:35 Released

ID: 225768.0, MPI für molekulare Genetik / Department of Human Molecular Genetics
Regulation of the MID1 protein function is fine-tuned by a complex pattern of alternative splicing
Authors:Winter, Jennifer; Lehmann, Tanja; Krauß, Sybille; Trockenbacher, Alexander; Kijas, Zofia; Foerster, John; Suckow, Vanessa; Yaspo, Marie-Laure; Kulozik, Andreas; Kalscheuer, Vera M.; Schneider, Rainer; Schweiger, Susann
Date of Publication (YYYY-MM-DD):2004-03-31
Title of Journal:Human Genetics
Journal Abbrev.:Hum. Genet.
Issue / Number:6
Start Page:541
End Page:552
Copyright:© Springer
Review Status:not specified
Audience:Experts Only
Abstract / Description:Clinical features of Opitz BBB/G syndrome are confined to defects of the developing ventral midline, whereas the causative gene, MID1, is ubiquitously expressed. Therefore, a non-redundant physiological function of the MID1 product appears to be developmentally restricted. Here, we report the identification of several alternative MID1 exons in human, mouse and fugu. We show that splice variants of the MID1 gene that are comparable in terms of function occur in the three organisms, suggesting an important role in the regulation of the MID1 protein function. Accordingly, we observed differential MID1 transcript patterns in a tissue-specific manner by Northern blot and RT-PCR. The identified splice variants cause loss-of-function effects via several mechanisms. Some introduce a stop codon followed by a novel poly(A+) tail, leading to the formation of C-terminally truncated proteins. Dominant negative effects through altered binding to the MID1-interacting protein agr4 in vitro could be demonstrated in a couple of cases. Others carry premature termination codons without poly(A+) tails. These are degraded by nonsense mediated mRNA decay (NMD). Our data reveal a mechanism conserved in human, mouse and fugu that regulates developmentally restricted MID1 activity and suggest NMD to be critical in the translational regulation of a ubiquitously transcribed mRNA.
Comment of the Author/Creator:Original Investigation.

Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00439-004-1114-x
External Publication Status:published
Document Type:Article
Communicated by:Hans-Hilger Ropers
Affiliations:MPI für molekulare Genetik
External Affiliations:Institute of Biochemistry, University Innsbruck, Innsbruck, Austria;
Klinik für Dermatologie, Charité-Hospital, Berlin, Germany;
University Hospital, Heidelberg, Germany.