Human Molecular Genetics Advance Access originally published online on October 14, 2003
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Human Molecular Genetics, 2003, Vol. 12, No. 23 3181-3194
DOI: 10.1093/hmg/ddg345
© 2003 Oxford University Press
Plectin 5'-transcript diversity: short alternative sequences determine stability of gene products, initiation of translation and subcellular localization of isoforms

Institute of Biochemistry and Molecular Cell Biology, University of Vienna, Vienna Biocenter, Dr. Bohrgasse 9, A-1030 Vienna, Austria
Received August 29, 2003; Accepted October 6, 2003
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 ß4-binding in some isoforms. The small alternative N-terminal sequences (5180 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.
* To whom correspondence should be addressed. Tel: +43 1427752851; Fax: +43 1427752854; Email: wiche{at}abc.univie.ac.at
Present address: Division of Gynecology, Molecular Oncology Group, Department of Obstetrics and Gynecology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
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