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Two overlapping reading frames in a single exon encode interacting proteins--a novel way of gene usage
M Klemke1, R H Kehlenbach, W B Huttner
1Department of Neurobiology, Interdisciplinary Centre of Neuroscience, University of Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
The EMBO Journal
|July 12, 2001
Summary
Researchers discovered a new gene usage mechanism in rats. An alternative open reading frame (ORF) in the XL-exon gene encodes a novel protein, ALEX, which binds to XLalphas, revealing unprecedented gene expression in mammals.
Area of Science:
- Molecular Biology
- Genetics
- Neuroendocrinology
Background:
- The XL-exon of the rat XLalphas/Galphas gene encodes the XL-domain, part of the XLalphas G-protein subunit.
- XLalphas is a neuroendocrine-specific protein crucial in cellular signaling.
Purpose of the Study:
- To investigate novel features within the XL-exon.
- To identify alternative protein products from the XLalphas/Galphas gene.
Main Methods:
- Analysis of the XL-exon's open reading frames (ORFs).
- Identification and characterization of a novel protein (ALEX) encoded by an alternative ORF.
- Investigation of ALEX expression and localization in neuroendocrine cells.
- Examination of the interaction between ALEX and XLalphas.
Main Results:
- A previously unrecognized alternative ORF (>1 kb) was found within the XL-exon, overlapping the XL-domain ORF.
- This alternative ORF encodes ALEX, a basic, proline-rich protein of 356 amino acids.
- Both XLalphas and ALEX are translated from the same mRNA and expressed in neuroendocrine cells.
- ALEX is localized to the plasma membrane and binds to the XL-domain of XLalphas.
Conclusions:
- A novel gene usage mechanism, unprecedented in mammalian genomes, has been identified.
- The XL-exon can produce two distinct proteins, XLalphas and ALEX, from a single mRNA.
- ALEX represents a new protein interacting with XLalphas, potentially modulating its function.