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

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.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.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 exons may or may not be present thus changing the peptide sequence and properties [12]. The alternative use of polyA signals also has effects, for instance, on RNA stability [13,14].The mechanisms described above all have in common the fact that the elements involved are associated only with the gene being tr