Figure 1

Schematics of the single Nrf1 gene with its products of multiple transcript and polypeptide isoforms.
Diagrammatic representation of chromosomal locations of the Nfe2l1 gene loci (expressed as Nrf1, TCF11 and/or LCR-F1) in both the mouse (a) and human (b), with different numbers of their exons. The left-handed side shows different lengths of multiple transcripts with altered numbers of the exons indicated, which were predicted to translate various protein isoforms shown on the right-handed side. Of note, exon 2a is generally considered to be untranslated, but indeed is bioinformatically predicted to contain an upstream open reading frame (uORF), exons 3 to 5 located within the main ORF can also be allowed for no, partial or complete translation insomuch as to give rise to various lengths of distinct protein forms. (c) The schematic shows that production of multiple isofoms is predominantly attributable to alternative translation from mRNA variants arising from three different transcription start sites (e.g. to yield Nrf1α/TCF11, Nrf1ΔN and Nrf1β), alternative splicing of longer transcripts (e.g. to remove exon 4 in Nrf1α and Nrf1ΔN) and the putative regulation of the long 3′-untranslational region (UTR) containing two polyA tail signals. The transcriptional expression is directed by arrows, whilst both untranslated and translated exons were represented by light and dark blue boxes, respectively. The site of the gene manipulated is specifically positioned in close proximity to the first translation start codons of Nrf1α.