Human Molecular Genetics Advance Access published online on October 14, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddg345
© 2003 by Oxford University Press
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1 Institute of Biochemistry and Molecular Cell Biology, University of Vienna, Vienna Biocenter, Dr. Bohrgasse 9, A-1030 Vienna, Austria; Division of Gynecology, Molecular Oncology Group, Department of Obstetrics and Gynecology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria
* To whom correspondence should be addressed. E-mail: wiche{at}abc.univie.ac.at.
Plectin is a large cytoskeletal linker protein expressed as several different isoforms from a highly complex gene. This transcript diversity is mainly caused by short 5'-sequences contained in alternative first exons. To elucidate the influence of these sequence differences and to determine potential differential functionality of the resulting protein forms, we conducted a systematic investigation of plectin isoforms on transcript and protein levels. Isoform expression was highly dependent on the different 5'-ends, largely due to effects of the 5'-untranslated regions. Initiation of translation downstream of the expected start site led to loss of actin- and integrin
Article
Plectin 5'-transcript diversity: short alternative sequences determine stability of gene products, initiation of translation, and subcellular localization of isoforms
2 Institute of Biochemistry and Molecular Cell Biology, University of Vienna, Vienna Biocenter, Dr. Bohrgasse 9, A-1030 Vienna, Austria
Abstract 
4-binding in some isoforms. The small alternative N-terminal sequences (5-180 residues) profoundly affected the subcelluar localization of this >500 kDa protein. Specifically, plectin 1f was concentrated at focal adhesion contacts and plectin 1b was exclusively targeted to mitochondria, providing a connection of these organelles to intermediate filaments. Thus, with plectin as a model, we demonstrate a role for 5'-untranslated regions and alternative 5'-splicing as an important regulatory mechanism of protein expression and protein function.
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