Alternative pre-mRNA processing regulates cell-type specific expression of the IL4l1 and NUP62 genes

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Here we provide evidence that the<jats:italic>IL4I1</jats:italic>gene is specifically transcribed from the apparent promoter of the upstream<jats:italic>NUP62</jats:italic>gene, and that the first two exons of<jats:italic>NUP62</jats:italic>are also contained in the novel<jats:italic>IL4I1_2</jats:italic>variant. While expression of<jats:italic>IL4I1</jats:italic>driven from its previously described promoter is found mostly in B cells, the expression driven by the<jats:italic>NUP62</jats:italic>promoter is restricted to cells in testis (Sertoli cells) and in the brain (e.g., Purkinje cells). Since<jats:italic>NUP62</jats:italic>is itself ubiquitously expressed, the<jats:italic>IL4I1_2</jats:italic>variant likely derives from cell type specific alternative pre-mRNA processing.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Comparative genomics suggest that the promoter upstream of the<jats:italic>NUP62</jats:italic>gene originally belonged to the<jats:italic>IL4I1</jats:italic>gene and was later acquired by<jats:italic>NUP62</jats:italic>via insertion of a retroposon. Since both genes are apparently essential, the promoter had to serve two genes afterwards. Expression of the<jats:italic>IL4I1</jats:italic>gene from the "<jats:italic>NUP62</jats:italic>" 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.</jats:p></jats:sec>