Alternative pre-mRNA processing regulates cell-type specific expression of the IL4l1 and NUP62 genes
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BioMed Central
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Research article
Alternative pre-mRNA processing regulates cell-type specific expression of the IL4l1 and NUP62 genes Stefan Wiemann*†, Anja Kolb-Kokocinski† and Annemarie Poustka Address: Molecular Genome Analysis, German Cancer Research Center, Im Neuenheimer Feld 580, Heidelberg, 69120, Germany Email: Stefan Wiemann* - [email protected]; Anja Kolb-Kokocinski - [email protected]; Annemarie Poustka - [email protected] * Corresponding author †Equal contributors
Published: 19 July 2005 BMC Biology 2005, 3:16
doi:10.1186/1741-7007-3-16
Received: 08 March 2005 Accepted: 19 July 2005
This article is available from: http://www.biomedcentral.com/1741-7007/3/16 © 2005 Wiemann et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: Given the complexity of higher organisms, the number of genes encoded by their genomes is surprisingly small. Tissue specific regulation of expression and splicing are major factors enhancing the number of the encoded products. Commonly these mechanisms are intragenic and affect only one gene. Results: Here we provide evidence that the IL4I1 gene is specifically transcribed from the apparent promoter of the upstream NUP62 gene, and that the first two exons of NUP62 are also contained in the novel IL4I1_2 variant. While expression of IL4I1 driven from its previously described promoter is found mostly in B cells, the expression driven by the NUP62 promoter is restricted to cells in testis (Sertoli cells) and in the brain (e.g., Purkinje cells). Since NUP62 is itself ubiquitously expressed, the IL4I1_2 variant likely derives from cell type specific alternative pre-mRNA processing. Conclusion: Comparative genomics suggest that the promoter upstream of the NUP62 gene originally belonged to the IL4I1 gene and was later acquired by NUP62 via insertion of a retroposon. Since both genes are apparently essential, the promoter had to serve two genes afterwards. Expression of the IL4I1 gene from the "NUP62" promoter and the tissue specific involvement of the pre-mRNA processing machinery to regulate expression of two unrelated proteins indicate a novel mechanism of gene regulation.
Background Many mechanisms for the alternative use of promoters, exons and polyadenylation signals within genes are known to significantly contribute to the complexity of the transcriptome [1-6]. These variations increase the number of products that can be generated from the currently recognized 20,000 – 30,000 protein-coding genes of the human genome [7]. For example, alternative promoters are used to confer specificity of mRNA expression in time and space [8,9] and of mRNA translation [10]. Often the N-terminal ends of proteins are altered to generate or
remove signal sequences for protein localization [11]. Central exon
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