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  Regulation of the MID1 protein function is fine-tuned by a complex pattern of alternative splicing

Winter, J., Lehmann, T., Krauß, S., Trockenbacher, A., Kijas, Z., Foerster, J., et al. (2004). Regulation of the MID1 protein function is fine-tuned by a complex pattern of alternative splicing. Human Genetics, 114(6), 541-552. doi:10.1007/s00439-004-1114-x.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8897-C Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8898-A
Genre: Journal Article
Alternative Title : Hum. Genet.

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 Creators:
Winter, Jennifer1, Author              
Lehmann, Tanja2, Author
Krauß, Sybille2, Author
Trockenbacher, Alexander, Author
Kijas, Zofia2, Author
Foerster, John, Author
Suckow, Vanessa3, Author              
Yaspo, Marie-Laure4, Author              
Kulozik, Andreas, Author
Kalscheuer, Vera M.5, Author              
Schneider, Rainer1, Author              
Schweiger, Susann1, Author              
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              
2Max Planck Society, ou_persistent13              
3Signal Transduction in Mental Retardation and Pain (Tim Hucho), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479646              
4Human Chromosome 21 (Marie-Laure Yaspo), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479652              
5Chromosome Rearrangements and Disease (Vera Kalscheuer), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479642              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2004-03-31
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: eDoc: 229504
DOI: 10.1007/s00439-004-1114-x
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Title: Human Genetics
  Alternative Title : Hum. Genet.
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 114 (6) Sequence Number: - Start / End Page: 541 - 552 Identifier: ISSN: 0340-6717